bioworld - frontiermeds.com, of boston, said it is planning a proposed follow-on public offering of...

BioWorldJune 26 2019

Volume 30 No 123

copy 2019 Clarivate Analytics

The news source of record covering the development of innovative human therapies Actionable Intelligence bull Incisive Analysis

Lights camera hellip auction Query $63B showstopper in Abbviersquos Allergan grabBy Randy Osborne Staff Writer

Abbvie Incrsquos agreement to take over Allergan plc in a cash and stock deal worth about $63 billion jarred Wall Street and set pundits mulling the price tag ndash seen by some as too low ndash along with the prospects for a satisfying marriage as pipelines are sorted out The value of the pact is based on the closing price of Abbvie shares (NYSEABBV) of $7845 Monday Dublin-based Allergan shareholders will receive 08660 Abbvie shares and $12030 in cash for each

Acer derailed by CRL seeking new trial for vEDS drugBy Michael Fitzhugh News Editor

Shares of Acer Therapeutics Inc (NASDAQACER) fell 786 to $412 Tuesday after the FDA issued a complete response letter (CRL)calling for the company to conduct an ldquoadequate and well-controlled trialrdquo to determine whether the orphan-designated beta-blocker Edsivo (celiprolol) reduces the risk of clinical events in patients with vascular Ehlers-Danlos syndrome (vEDS) an inherited connective tissue disorder Chris Schelling CEO and founder of the Newton Mass-based company said his team expects to respond to the regulator in the third quarter of this year (See BioWorld Sept 28 2018)ldquoAlthough the marketing application was based on data from a small study with 53 patients a recent long-term retrospective study has also demonstrated that Edsivo is associated with significant improvements in survival and hospitalization rates for acute arterial bleedsrdquo wrote

Spainrsquos Sanifit preps for phase III calciphylaxis trial with $809M private roundBy Nuala Moran Staff Writer

LONDON ndash Laboratoris Sanifit SL has closed Spainrsquos largest ever private biotech round raising euro722 million (US$809 million) to fund phase III development of SNF-472 in the treatment of calciphylaxis an orphan disease that occurs in end-stage renal disease patients on dialysisThe new money is made up of a euro552 million series D and the capitalization of euro17 million of convertible bonds The fundraising was led by existing investor Caixa Capital Risk a Spanish venture capital firm and attracted Columbus Venture Partners and Alta Life Sciences as new investorsExisting shareholders who put $41 million in the September 2015 series C including Lundbeckfonden Ventures Ysios Capital Forbion Capital Partners Gilde Partners and Andera Partners followed on

SQZ adds RBCs in Erytech immunotherapy deal for $57M up front milestonesBy Cormac Sheridan Staff Writer

DUBLIN ndash Itrsquos the kind of deal that says a lot more about a companyrsquos scientific chops than about its financial prospects but Erytech Pharma SA entered an agreement with SQZ Biotechnologies Inc under which the latter firm will have exclusive

Terns gains Chinese rights to Genfitrsquos NASH treatment in $228M collaborationBy David Ho Staff Writer

HONG KONG ndashTerns Pharmaceuticals Inc a company based in China and the US entered a licensing and collaboration agreement with French company Genfit SA to develop and commercialize elafibranor in development

See Abbvie page 3

See Sanifit page 5

See Vesalius page 8

See Terns page 7

See Frontier page 9See Acer page 4

Frontier Medicines launches with a $67M series A roundBy Lee Landenberger Staff WriterFrontier Medicines Corp closed on a series A preferred stock financing round of $67 million for honing its pipeline and prepping for the clinicldquoWe have a pipeline wersquore developing now but we havenrsquot disclosed our targetsrdquo Chris Varma

See Erytech page 6

Vesalius closes third life sciences fund at $137MBy Cormac Sheridan Staff WriterDUBLIN ndash Two years after announcing a first close Vesalius Biocapital Partners SagraveRL has topped out its third fund Vesalius Biocapital III (VB-III) at euro120 million (US$1366 million)The new fund will follow a similar investment strategy to that pursued by its predecessor funds with about half of the cash going to

Newco News

Wednesday June 26 2019 BioWorld Page 2 of 15

BioWorldBioWorld (ISSN 1541-0595) is published every business day by Clarivate Analytics

Opinions expressed are not necessarily those of this publication Mention of products or services does not constitute endorsement

copy 2019 Clarivate Analytics All rights reserved Republication or redistribution of Clarivate Analytics content including by framing or similar means is prohibited without the prior written consent of Clarivate Analytics Clarivate and its logo are trademarks of the Clarivate Analytics group

Our newsroom Lynn Yoffee (News Director) Jennifer Boggs (Managing Editor) Peter Winter (BioWorld Insight Editor) Michael Fitzhugh (News Editor) Anette Breindl (Senior Science Editor) Mari Serebrov (Regulatory Editor) Amanda Lanier (Managing Editor) Karen Pihl-Carey (Analyst) Ann Marie Griffith (Production Editor)

Staff writers Randy Osborne Shannon Ellis John Fox Nuala Moran Brian Orelli Alfred Romann Tamra Sami Cormac Sheridan

Practical informationFor sales inquiries httpsclarivatecomproductsbioworld In North America call 1-855-260-5607 Outside of the US and Canada call +44-203-684-1797

For customer service support httpssupportclarivatecomLifeSciences In North America call 1-800-336-4474 Outside of the US and Canada call +44-203-684-1796

For ad rates and information contact Adam Lubas at (929) 246-3800 or email AdamLubasClarivatecom

For photocopy rights or reprints contact Adam Lubas at (929) 246-3800 or email AdamLubasClarivatecom

Send all press releases and related information to newsdeskbioworldcom

Business office John Borgman (Director of Commercial Competitive Intelligence) Donald Johnston (Senior Marketing Communication Director Life Sciences)

Contact usJennifer Boggs (770) 880-3631 | John Borgman (831) 462 2510 | Anette Breindl (770) 810-3134 | Michael Fitzhugh (770) 810-3064 | Donald Johnston (678) 641-0970 | Nuala Moran 44-7778-868-579 | Randy Osborne (770) 810-3139 | Mari Serebrov (770) 810-3141 | Cormac Sheridan 353-87-6864323 | Peter Winter (770) 810-3142 | Lynn Yoffee (434) 964-4011

Financings

Akero Therapeutics Inc of San Francisco said it closed its IPO of 66 million shares including the exercise in full by the underwriters of their option to purchase up to 862500 additional shares at $16 each for aggregate gross proceeds of approximately $1058 million The companyrsquos common stock is listed on Nasdaq under the ticker symbol AKROArqule Inc of Burlington Mass said it priced an underwritten public offering of 925 million shares at $975 each The underwriters have been granted a 30-day option to purchase up to an additional 138 million shares of its common stock The gross proceeds excluding any exercise by the underwriters of their option are expected to be approximately $902 million and it intends to use net proceeds to fund clinical programs and for general corporate purposesArtelo Biosciences Inc a La Jolla Calif-based company developing medicines targeting the endocannabinoid system announced the closing of its previously announced underwritten public offering of about 13 million units at $615 per unit Each unit consisted of one share of common stock (NASDAQARTL) and one warrant to purchase one share of common stock at an exercise price of $646 per share The company received gross proceeds of $8 million In connection with the offering it conducted a reverse split of its common stock at a ratio of 1-for-8 Company shares fell 33 cents Tuesday to close at $460Eloxx Pharmaceuticals Inc of Waltham Mass said it closed its underwritten public offering of 383 million shares of its common stock which includes the full exercise of the underwritersrsquo option to purchase an additional 500000 shares at $9 per share The gross proceeds were approximately $345 million and the net proceeds will be used to fund the continued clinical development of ELX-02 in cystic fibrosis and cystinosis to accelerate development of early stage programs and for working

capital and other general corporate purposesGamida Cell Ltd of Boston said it is planning a proposed follow-on public offering of approximately $30 million of its ordinary shares In addition the underwriters will be granted a 30-day option to purchase up to $45 million of additional ordinary sharesKrystal Biotech Inc of Pittsburgh said it priced an underwritten public offering of 25 million shares of its common stock at $40 each and the underwriters have been granted a 30-day option to purchase up to an additional 375000 shares The gross proceeds are expected to be approximately $100 millionMirati Therapeutics Inc of San Diego said it intends to offer and sell subject to market and other conditions $75 million of shares of its common stock in an underwritten public offering The company expects to grant the underwriters a 30-day option to purchase up to an additional $1125 million of shares of its common stockSareum Holdings plc of Cambridge UK raised gross proceeds of pound513200 (US$651400) through a placement by Hybridan LLP of 1283 million new ordinary shares (AIMSAR) of 0025 pence each in the capital of the company at 04 pence per share It said net proceeds will be used to advance the companyrsquos preclinical TYK2JAK1 assets SDC-1801 and SDC-1802 as well as for working capital purposes Tetra Bio-Pharma Inc of Ottawa Ontario said it priced its marketed public offering of units at a CA30 cents (US23 cents) per unit which will consist of one common share and one common share purchase warrant that will entitle its holder to acquire one common share at an exercise price of CA40 centsThe Medicines Co of Parsippany NJ said it launched a public offering of $150 million of shares of its common stock In addition the underwriters will be granted a 30-day option to purchase up to an additional $225 million of shares of common stock The company expects to use the net proceeds to fund its development of inclisiran a cholesterol-lowering GalNAc-conjugated RNA interference therapeutic and for general corporate purposes



Allergan share they hold for a consideration of $18824 per Allergan share The payout represents a 45 premium to Allerganrsquos previous close The firmrsquo stock (NYSEAGN) closed Tuesday at $16243 up $3286 or 254 Abbvie ended at $6570 down $1275 or 163SVB Leerinkrsquos Marc Goodman covering Allergan said that ldquogiven the multiyear stock weakness we are not surprised that one of the large pharma companies has made a bidrdquo on the firm but he found $188 per share ldquotoo low We canrsquot believe that Allergan is not being taken out at least at $200rdquo he wrote in a report asking rhetorically whether the deal ldquowas [the result of] a process or is Abbvie opportunistically pursuing a wounded stockrdquo If the latter other suitors could surface ldquoEither way it looks as though the Allergan shareholders will be finally be rewarded for their patiencerdquo he saidPiper Jaffrayrsquos David Amsellem saw it differently ldquoWe will start by saying that this was certainly not the ending that we had envisioned for Allerganrdquo he wrote in a report ldquoAt the risk of raining on the parade we would add that the fact that this senior leadership team managed to find a way to exit gracefully should not and does not obscure years of questionable acquisitions poor capital allocation (particularly the heavy emphasis on buybacks) and an overall lack of strategic directionrdquo He said Abbvie for its part gains ldquoa veritable mixed bag a durable consumer-facing cash pay business (still high-quality warts and all) but also a pharma business that is brimming with uncertainty (ie losses of exclusivities competitivepayer headwinds)rdquo Amsellem maintained his neutral rating on Allergan deeming the arrangement ldquothe lifeline to end all lifelinesrdquoEvercore ISI held a webinar for investors during which analyst Joshua Schimmer went down the middle with his opinion on price saying that the arrangement ldquodoesnrsquot seem like an obviously cheap deal [and it] doesnrsquot look like an obviously expensive dealrdquo and that Abbvie needs to execute properly with assets the company is acquiring ldquoClearly itrsquos not the deal that any of us were looking for ndash we were hoping to see more of a pipeline upgrade as opposed to a larger-scale transaction like thisrdquo he said ldquoSentiment on Abbvie was already extremely poor it just got even worserdquo Regarding Allergan he found it ldquointeresting that therersquos hyper-focus on Botox [onabotulinumtoxinA] competition and hyper-focus on the opioid-litigation concern which doesnrsquot really seem to be much of a big dealrdquo Schimmer conceded that the move ldquostrategically fits with Abbviersquos effort to always have the best and first-in-class assetsrdquo even if the buyout gets the firm into ldquoall sorts of other verticals that theyrsquore not used to But if yoursquore going to get into other verticals this is certainly the way to do itrdquoNorth Chicago-based Abbvie painted a bright picture saying it expects the buyout to provide annual pre-tax synergies and other cost reductions of at least $2 billion in the third year while leaving investments in key growth franchises untouched The company plans to optimize the research and early stage portfolio and

reduce overlapping RampD resources by about 50 which should mean more efficiencies in driving efficiencies in selling general and administrative expenses including sales and marketing and central support function costs for about a 40 improvement while getting rid of redundancies in the manufacturing and supply chain and leveraging procurement spend to reach about a 10 upside ldquoSignificantrdquo annual operating cash flow is expected by Abbvie too for a debt reduction target of $15 billion to $18 billion before the end of 2021

Humira independence dayDuring a conference call with investors Abbvie CEO Richard Gonzalez said his firm had ldquoworked on this strategy with our board for about a yearrdquo examining options ldquoone of which was a larger transaction like this And when we made the decision [on] the best path to go forward then we spent a large amount of time analyzing product-by-product the Allergan portfolio to ensure that it fit the objectives that we had Certainly one of the things that we looked at carefully is Botox from the perspective of both what was the risk of a biosimilar coming to the market and what was the risk of other branded competitive alternatives entering the marketrdquo some of which already have arrived ldquoIf you look carefully at how Allergan has performed Irsquod say theyrsquove done a good very good job of protecting Botox Theyrsquove lost some share but itrsquos relatively modestrdquo Laura Schumacher chief legal officer said Abbvie is ldquovery familiar with this [opioid] litigationrdquo which as the opioid epidemic spread also has targeted other companies ldquoItrsquos important to note that Allergan had a very small and declining market share in branded opioid for the past 20 years Our view is that this litigation is in early stages and the legal theories have not been challenged through the legal process yet In the one case that has proceeded to trial all but one of the plaintiffrsquos legal theories were dropped before trial and there are two state courts already that have rejected the plaintiffrsquos theories It will be important to see how the trial plays out and also how the appellate process plays out Wersquore confident in our ability to handle complex litigation and we have a long track record of achieving both favorable trial verdicts as well as settlementsrdquoWhen the takeover deal is done ndash early next year the companies hope ndash Abbvie shareholders will own about 83 of Abbvie on a fully diluted basis with Allergan having the remainder Abbvie will continue to be incorporated in Delaware and keep its executive offices in North Chicago with Gonzalez remaining in place Two members of Allerganrsquos board including chairman and CEO Brent Saunders will join AbbviersquosLeerinkrsquos Geoffrey Porges said in a report that the Allergan buy surprised him but ldquois consistent with Abbviersquos intention to diversify away from their dependencerdquo on Humira (adalimumab) its human IgGl monoclonal antibody specific for human tumor necrosis factor that was first approved for rheumatoid arthritis in late 2002 ldquoThe transaction takes advantage of Abbviersquos dividend yield discounted multiple and low borrowing cost and significantly reduces [the companyrsquos] future dependence on their immunology franchiserdquo To him the paired entity seems ldquolikely to be able to maintain Abbviersquos impressive track record of dividend growthrdquo with ldquoeven modest

AbbvieContinued from page 1

See Abbvie page 4



David Sherman an analyst with Lifesci Capital LLC a firm that received compensation from Acer for producing the reportAcer submitted an NDA seeking approval to market Edsivo for the treatment of vEDS in patients with a confirmed type III collagen (COL3A1) mutation in October 2018 In December the agency accepted it granting a requested priority review making the CRL ldquoa surpriserdquo Sherman wroteThe company had already made what Schelling said in May was ldquosignificant progress in preparing for a potential launch of Edsivordquo including the addition of commercial and medical affairs leaders with extensive experience in launching orphan drugs What Schelling and his team will do with those resources in the meantime as they determine their next steps was unclear Tuesday as the company declined to provide further commentEhlers-Danlos syndrome (EDS) is a group of hereditary disorders of connective tissue of which vEDS is the most severe subtype Patients suffer from life threatening arterial dissections and ruptures as well as intestinal and uterine ruptures according to Acer The average mortality is 51 years of age Treatment and management of the condition is focused on preventing serious complications and relieving signs and symptoms according to the NIHrsquos Genetic and Rare Diseases Information Center There is no known cure nor any competing therapies in development at this time according to CortellisAn Acer-commissioned patient-finder study identified 4169 vEDS patients in the US the company said Based on that information the company estimates the prevalence of

phenotypically defined vEDS in the US could be greater than one in 45000Edsivo is a repurposed formulation of celiprolol a cardioselective beta-blocker that up-regulates collagen synthesis through TGF-beta In addition to providing the FDA with the earlier clinical research on celiprolol the company also supplied long-term data from a cohort of COL3A1-positive vEDS patients published in the Journal of the American College of Cardiology The published data includes up to 17 years of safety data in the patient population with survival curve analysis showing that those patients not treated with celiprolol had a significantly worse outcome than celiprolol-treated patients Additional work underway at Acer that the company highlighted in its most recent quarterly update has included the in-licensing of osanetant in December from Sanofi SA and preparation of a bridging study for ACER-001 an immediate-release formulation of sodium phenylbutyrate with an initial indication in urea cycle disordersAcer and Opexa Therapeutics Inc of The Woodlands Texas agreed to merge in the summer of 2017 Shareholders of Acer gained about 88 of Opexarsquos outstanding stock on a pro forma basis with Opexa shareholders ending up with the rest An investor syndicate led by TVM Capital Life Sciences and comprising existing Acer investors along with new investors committed to put about $157 million into Acer at the time The merger was completed the following SeptemberThe company raised $46 million through an underwritten public offering in August 2018 It had $318 million in cash and cash equivalents at the end of March 2019 s

AcerContinued from page 1


efficienciesrdquo helping to drive pro forma earnings per share growth ldquoabove the pharmaceutical industry average which should be attractive to some investorsrdquo At the same time he called the deal ldquoyet another transaction driven by diversification scale and low borrowing costs rather than portfolio or top-line synergiesrdquo and predicted Abbvie would ldquotrade poorly on this announcement and then be dependent on investorsrsquo expectations for counter-offers or other risksrdquo to the agreement He noted that Allergan ldquohas been dogged by disappointing RampD performance and unrealistic expectations for pipeline programs and Abbvie has suffered from some of the same issuesrdquoOn the subject of counter-offers RBCrsquos Randall Stanicky said analysts at his firm ldquodo not expect anyone coming in over the toprdquo New York-based Pfizer Inc and Johnson amp Johnson of New Brunswick NJ ldquohave come up as potential suitorsrdquo but neither seems a solid candidate ldquoand this deal price appears fair based on our $191 break-up valuation While this take-out is not a lsquowinrsquo for Allergan holders per se we think itrsquos the best option given persisting earnings pressures and what would likely be a drawn-out break-up processrdquo s

The dispute over who invented the CRISPRCas9 gene editing system for eukaryotic cells took a new turn Tuesday with the US Patent Trial and Appeal Board (PTAB) declaring an interference between 10 University of California (UC) patent applications and several US patents already issued to the Massachusetts Institute of Technology Broad Institute The action jeopardizes 13 of the Broadrsquos 15 CRISPRCas9 US patents as well as one application according to UC officials Last September the US Court of Appeals for the Federal Circuit upheld a PTAB judgment that had found no interference-in-fact between UC claims and the patents already issued to Broad saying the claims werenrsquot directed to the same subject matter Broad had limited its claims to use in eukaryotic cells whereas the claims in UCrsquos application didnrsquot refer to a particular cell type or environment However the Federal Circuit made no specific determination on priority of invention of genome editing within eukaryotic cells UC said Following that ruling UC was awarded six US patents for CRISPR technologies in other cellular or noncellular settings and it has six additional applications set to issue in the coming weeks UC holds more than 50 CRISPR patents worldwide (See BioWorld Sept 11 2018)

Regulatory front



In addition to a phase III USEuropean trial in 65 to 70 patients with calciphylaxis the new money will fund work on manufacturing scale-up of SNF-472 (hexasodium phytate) and the completion of a phase IIb study in the broader indication of cardiovascular calcification in hemodialysis patientsBefore raising the series C Palma Majorca-based Sanifit had raised only euro6 million from local funds grants and private individuals since it was formed in 2007Assuming positive clinical results in the phase III calciphylaxis study Sanifit now has enough money to see it through to FDA and EMA marketing submissions

ldquoItrsquos an amazing storyrdquo said Joan Perello co-founder and CEO ldquoWe succeeded last time with phase I data Now wersquove got two parallel phase IIs on [the basis of] the last raise and funding for the phase IIIrdquo he told BioWorld SNF-472 is the only molecule based on university research carried out in Spain to have made it through to phase III development Perello saidCalciphylaxis is a severe and usually fatal disorder in which calcium is deposited in the small peripheral blood vessels of the limbs and abdomen That leads onto the

formation of painful skin ulcers and the necrosis of surrounding tissues Calcification progresses rapidly and there is a one-year mortality rate of 55The phase II open-label study which reported last year assessed the effect on wound healing in 14 patients They were treated with an intravenous formulation of SNF-472 during hemodialysis three times a week for up to 12 weeks There were clinically and statistically significant improvements in wound healing and pain and SNF-472 was generally well-toleratedThe phase III trial will open in Spain and the UK by the end of the year Centers are being evaluated elsewhere in Europe and in the US big hemodialysis centers will be an important source of patients Perello saidAs recruitment gets underway in the phase III trial in calciphylaxis Sanifit is expecting the read-out from the phase IIb trial of SNF-472 in the treatment of cardiovascular calcification in end-stage renal disease patientsMost patients at the end stage of renal disease have accelerated calcification in the coronary artery That correlates with higher cardiovascular risk and cardiovascular disease is the most common cause of death There are no approved therapies and it is estimated there are 25 million patients worldwideThe 350-patient double-blind placebo-controlled 52-week phase IIb completed last AugustSNF-472 works by preventing the formation of microcrystals of calcium hydroxyapatite the penultimate step in the pathway leading to vascular calcification In the phase IIb the endpoint

is the drugrsquos effect on cardiovascular calcification as assessed by coronary artery calcification scoreldquoIn preclinical models if calcification is blocked or slowed down [cardiovascular] disease can be reversed But itrsquos not the drug doing it from a mechanistic point of viewrdquo said Perello The phase IIb data will be an important inflection point for Sanifit ldquoAt the year end with data in hand we will look for [commercialization] partnersrdquo Perello said The next step beyond that will be to conduct a phase III to see if SNF-472 reduces cardiovascular events in end stage renal disease s

SanifitContinued from page 1

Joan Perello co-founder and CEO Laboratoris Sanifit

Wondering what you missed in BioWorld Insight

No lsquoRestrsquo for the DED as blockbuster wannabes jockey for leadThe hunt is on in earnest for a dry eye disease (DED) therapy to replace Allergan plcrsquos blockbuster Restasis (ciclosporin) which the Dublin-based firm sought to shield behind the protective estate of 27 patents including six the company famously assigned in 2017 to the Saint Regis Mohawk Tribe and then licensed back in perpetuity seeking to prevent their expiry in 2024 In November the US Federal Circuit upheld a Patent Trial and Appeal Board decision that invalidated the six patents for obviousness The Federal Circuit had ruled against tribal sovereign immunity a few months earlier While generics manufacturers wait in the wings the heir apparent to Restasis at least for now appears to be the small-molecule LFA1ICAM-1 antagonist Xiidra (lifitegrast) which Shire plc of Dublin advanced to market in the US after acquiring developer Sarcode Bioscience Inc Last month Novartis AG of Basel Switzerland placed a big bet on that outcome picking up the drug from debt-laden Takeda Pharmaceutical Co Ltd in a potential $53 billion deal after Takeda swallowed Shire last year for $62 billion But therersquos plenty of activity behind Xiidra in the phase IIIII DED pipeline

ASCO 2019 Beyond POLO string of ponies running on large DDR fieldOne of the highlights of the 2019 annual meeting of the American Society of Clinical Oncology (ASCO) earlier this month were results from the phase III POLO trial demonstrating that treatment with Lynparza (olaparib Astrazeneca plcMerck amp Co Inc) after platinum chemotherapy nearly doubled the progression-free interval (progression-free survival) in a group of 154 metastatic pancreatic cancer patients with germline BRCA mutations from 38 to 74 months Also roughly doubled was the proportion of patients who had not progressed after two years from 96 to 221

BioWorld subscribers can add BioWorld Insight for a special discounted rate Call 855-260-5607 in North America Outside of the US and Canada call +44-203-684-1797



access to Erytechrsquos red blood cell (RBC) platform for therapies that modulate the immune systemLyon France-based Erytech will receive $57 million in up-front and potential development regulatory and commercial milestone payments for a first product to emerge from the alliance It would receive up to $50 million in commercial milestones for each additional indication or product plus royalties on all product sales ldquoItrsquos a back-end-loaded dealrdquo Erytechrsquos chief business officer Jean-Seacutebastien Cleiftie told BioWorld ldquoIt doesnrsquot change our cash guidance for the yearrdquoThe deal highlights an underemphasized aspect of the companyrsquos Erycaps technology platform Long before the likes of Rubius Therapeutics Inc started to use RBCs as carriers of therapeutic or immunogenic payloads Erytech was doing just that It transiently exposes donor-derived RBCs to osmotic stress which temporarily disrupts the cell membrane to allow macromolecules such as enzymes or antigens to enterThe company has long focused on deploying RBCs as carriers of enzymes principally asparaginase for disrupting cancer metabolism by starving tumors of essential amino acids Encapsulating the enzyme within an RBC eliminates the risk of serious hypersensitivity reactions and also provides for an improved dosing regimenAfter more than a decade of clinical development however the company has struggled to get its product Graspa across the line It abandoned acute myeloid leukemia because of a phase IIb trial failure in 2017 Although it was undergoing regulatory review in Europe in acute lymphoblastic leukemia it decided to quit that indication this time last year given the rapidly shifting competitive landscape arising from the advent of CAR T

therapy (See BioWorld June 26 2018)Erytech still remains focused on the same product concept but has since shifted to solid tumors It has a phase III trial underway in pancreatic cancer and a phase II trial ongoing in triple-negative breast cancer It has never had the resources to pursue the immunotherapeutic potential of the platform at the same time although it has published preclinical proof of concept demonstrating its ability both to elicit antigen-specific immune response and to induce immune tolerance to self-antigens Rubius has a different approach to loading RBCs with therapeutic or immunogenic payloads It transfects immature RBC precursors and then promotes their differentiation into mature enucleated cells that retain the ability to express the protein of interest The other big difference between the two firms is their valuation Erytech is currently valued at its cash balance despite being in phase IIIRubius has yet to enter the clinic but it has already attained unicorn status ldquoItrsquos the curse of the pioneerrdquo said Cleiftie ldquoWe think have validated this approach to red blood cell-based therapeuticsrdquoThe present deal with Cambridge Mass-based SQZ covers immune-modulating therapies that employ RBC approaches ldquoItrsquos really joining our knowledge and experience with their platform capabilitiesrdquo Cleiftie said SQZ has rapidly sprung to prominence on the basis of its ability to transfect different cell types by subjecting them to physical pressure which temporarily disrupts the cell membrane Itrsquos the kind of agenda-setting firm that all too rarely emerges in EuropeThat it should perceive some value in Erytechrsquos platform may be of little immediate interest to Erytechrsquos investors but it validates the companyrsquos original vision even if it was never in a position to realize it in full s

ErytechContinued from page 1

After a US federal court granted the request of 44 states to unseal the documents in a lawsuit they had filed against Teva Pharmaceuticals Co Ltd and 19 of the nationrsquos largest generic drug manufacturers Maryland Attorney General Brian Frosh Monday released the full complaint against the drug companies The evidence that was made public includes emails among the manufacturers ldquocoordinating their response to a congressional inquiry emails enforcing lsquofair sharersquo and lsquoplaying nice in the sandboxrsquo market allocation lsquofluff pricingrsquo strategy and other brazen coordination to artificially inflate prices hinder competition and unreasonably restrain trade across the industryrdquo according to Frosh For instance one email exchange shows that when Heritage Pharmaceuticals Inc received a letter from Rep Elijah Cummings (D-Md) and Sen Bernie Sanders (I-Vt) in October 2013 as part of the lawmakersrsquo joint investigation into generic drug price increases Heritagersquos ldquooutside counsel immediately coordinated a response with counsel for Teva and Mylanrdquo Frosh said Heritagersquos counsel noted in an email to a redacted party that his colleagues at

Mylan NV and Teva had ldquoboth been in contact with GPhA on coordinating a response ndash and the consensus at this point is that the responses will be lsquopolite f-ursquo lettersrdquo Earlier this month the Eatontown NJ-based Heritage agreed to pay more than $7 million in criminal penalties and civil damages for its part in a US generics price fixing scheme Under a deferred prosecution agreement with the US Department of Justice (DoJ) Heritage admitted it conspired to fix prices rig bids and allocate customers for generic versions of glyburide a diabetes drug The agreement noted Heritagersquos cooperation with the ongoing DoJ investigation including the companyrsquos disclosure of information regarding antitrust violations involving other drugs

Regulatory front

BioWorld is on LinkedInwwwlinkedincomgroups3356116



for nonalcoholic steatohepatitis (NASH) and primary biliary cholangitis (PBC)Under the terms Lille France-based Genfit will receive an up-front payment of $35 million from Terns It will also be eligible to receive up to $193 million in potential clinical regulatory and commercial milestone payments bringing the total potential value of the deal to $228 million In return Terns would earn the exclusive rights to develop register and market elafibranor for both NASH and PBC in the greater China market That would encompass mainland China Hong Kong Macau and Taiwan Upon successful commercial launch of elafibranor for the treatment of NASH in the Chinese markets Genfit would then be entitled to receive midteen percentage royalties from Terns based on sales in the territoryldquoIn addition to its appealing mechanism of action elafibranor is well-positioned in an ongoing phase III program to demonstrate NASH resolution as defined by global regulatory authorities and to provide meaningful benefit for patients living with NASH and PBCrdquo said Weidong Zhong the president and CEO of TernsElafibranor is the most advanced drug candidate in Genfitrsquos pipeline The oral once-daily first-in-class drug is being evaluated in a pivotal phase III trial in NASH Genfit is also developing a new non-invasive and easy-to-access blood-based in vitro diagnostic test to identify patients with NASH who may be appropriate candidates for drug therapy Later this year Genfit plans to initiate a phase III trial in PBC following its positive phase II results Ternsrsquo Zhong stated that both sides are looking forward to a productive partnership to improve treatment options for patients living with chronic liver disease and mentioned ldquobuilding future combination NASH therapiesrdquo as part of the plansAnother component of the strategic partnership is that both companies will undertake joint RampD projects in liver disease including the development of elafibranor in combination with Ternsrsquo proprietary compoundsPascal Prigent executive vice president of marketing and commercial development at Genfit also indicated ldquoa strong level of confidencerdquo in the collaborationldquoPrivate players with know-how in one part of the world can replicate it in another regionrdquo Stuart Witchell the managing director of Berkeley Research Group (Hong Kong) Ltd told BioWorld ldquoHowever it is crucial to understand the nuances and challenges in each region and adapt sales approach as well as product to suit the local marketsrdquo And with Chinarsquos National Medical Products Administration increasingly requiring trial data from Chinese subjects it makes sense to have a partner on the ground there ldquoThe trajectory of Chinese health care market development is different from others There are many China-specific problems that the cautious investor must pay attention tordquo said WitchellBut it remains a market with great potential for innovative treatments for which Witchell predicts ldquofast growthrdquo

NASH competitionThe NASH market is certainly looking competitive in China In February Ascletis Pharma Inc and 3-V Biosciences Inc signed an exclusive licensing deal for 3-V Biosciencesrsquo FASN (fatty acid synthase) inhibitor TVB-2640 in greater China The candidate is now in phase II trials funded by that agreementThat same month Hangzhou-based Sciwind Biosciences Co Ltd raised about yen200 million (US$295 million) in a series A funding round The company focuses on biological treatments for NASH caused by diabetes or obesity Earlier this month Terns initiated a phase I trial for TERN-101 its farnesoid X receptor (FXR) agonist candidate for the treatment of NASH The trial is going on in the US and plans are being made for a China study too ldquoWersquove made significant progress this year advancing the development of our lead program TERN-101 as part of our dedicated approach to NASH a condition with no existing treatment optionsrdquo said Erin Quirk the chief medical officer of TernsQuirk said Terns will be evaluating the data from that trial later this yearTERN-101 was previously advanced through a phase I study by Eli Lilly and Co which first discovered and developed it The compound demonstrated clinical pharmacokinetic properties consistent with once-daily dosingTerns signed a global exclusive deal for the potent non-bile acid FXR agonist last year The firm presented preclinical data at The International Liver Congress 2019 in Vienna showing that TERN-101 reduces liver steatosis inflammation ballooning and fibrosis in a diet-induced obese mouse model of NASH s

TernsContinued from page 1

US President Donald Trump Monday signed into law the Pandemic and All-Hazards Preparedness (PAHPA) and Advancing Innovation Act providing the resources the nation needs to respond to natural disasters infectious diseases and terrorists Now in its third iteration PAHPA takes steps to beef up the nationrsquos medical countermeasure (MCM) enterprise modernize biosurveillance capabilities and improve accountability for the Strategic National Stockpile of MCMs The new law codifies coordination on MCMs across federal agencies so that the agencies can ldquomore easily bridge gaps avoid redundancy and set priorities in developing the medical products needed in national security emergenciesrdquo according to the Department of Health and Human Services (HHS) The law also reauthorizes the Project Bioshield Special Reserve Fund for 10 years bringing more certainty to a program thatrsquos been integral in developing 10 medical products that now have FDA approval and in adding 15 drugs vaccines and treatments to the stockpile HHS said PAHPA was first launched in 2006 in response to Hurricane Katrina Congressional leaders had planned to have the reauthorization in place last year before PAHPA II expired in September but a conflict between two senators stalled the effort for several months (See BioWorld May 24 2018)

Regulatory front



drug development with the rest being focused on medical technology diagnostics and digital health an area of growing importance (See BioWorld May 19 2017)The Luxembourg-based fund plans to invest the cash in 10 to 15 companies involved in either drug development medical technology diagnostics or digital health It has already participated in four financings across three early stage firms It is about to sign a deal with a fourth firm in the digital health arena next week managing partner Marc Lohrmann said ldquoWe are well on the way to deploying the capitalrdquo he told BioWorld The latest venture is focused on care management for chronically ill patientsVesalius is both a seed and a series A investor in Sword Health Inc a New York-based firm pioneering home-based physical therapy for people with musculoskeletal disorders by combining a digital interface with motion tracking technology and remote monitoring and assessment of each exercise session by clinical experts The company originated in Porto Portugal where it retains an operational base but it relocated to the US at the behest of Khosla Ventures which led its $8 million series A round in April Sword is tapping into a large market ndash musculoskeletal disorders it claims are the second biggest cost driver in US health care and lead to annual expenditure of $190 billionIn January Vesalius participated in a euro36 million series A round in Mecuris GmbH a Munich Germany-based developer of an online platform for customized 3D printing of orthotics and prosthetics Last September it invested euro4 million in a series A extension at Turku Finland-based Forendo Pharma Ltd which had previously raised euro8 million to take forward a portfolio of drug candidates for endometriosisIn the drug development arena Vesalius is largely agnostic ldquoLike everybody else we are swamped with oncology investment opportunitiesrdquo Lohrmann said ldquoThere we are still a bit cautiousrdquo he added The large ticket sizes combined with difficulties in patient recruitment onto clinical trials and rapidly evolving standard-of-care regimens in different indications all give it pause for thought ldquoWe are still waiting for the ideal candidate to arriverdquo he said Central nervous system disease particularly Alzheimerrsquos is another difficult area although the fund is not actively excluding any particular therapeutic domainsVesalius had originally set a hard-cap target of euro150 million but is ldquovery happyrdquo with euro120 million Lohrmann said That total is well ahead of its first two funds which raised euro154 million between themThe European Investment Fund the European Unionrsquos agency for funding small and medium-sized enterprises put euro30 million into VB-IIISeveral existing investors have repeated their participation but on a larger scale reflecting the general trend across European VC at presentOthers raising cash this year include Dublin-based Fountain

Healthcare Partners which raised a third fund of euro118 million last month In March Paris-based Seventure Partners disclosed that it had raised more than half of the target euro200 million for its second microbiome-focused fund Health for Life Capital II Also in March BPI France a state-backed investment bankand Paris-based Sanofi SA unveiled Innobio 2 a second public-private fund for investing in French life sciences firms It hadsecured $153 million at its first close but the total could exceed$280 million In the UK Cambridge Innovation Capital plcthe listed investment firm that backs Cambridge Universitylife science and technology spinouts raised pound150 million(US$1906 million) in new funding And earlier this month aFrench public-private university hospital consortium launched a $112 million regional seed fund First for startups focused on neurology and health care (See BioWorld June 17 2019)Germany as has long been the case remains bearish onbiotech despite the countryrsquos strong life sciences research base ldquoThere could be more money coming from institutionalinvestors in Germanyrdquo Lohrmann said ldquoThe strongestgeography is Germany closely followed by France andBeneluxrdquoSyndication remains an issue in Europe Lohrmann saidFinding investors who have the same vision of a firm and similar needs in terms of investment horizons is still difficult but the expanding universe of European VC funds with backing from the EIF and its sister organization the EuropeanInvestment Bank is opening up new access routes into theEuropean investor community s

VesaliusContinued from page 1 ldquoLike everybody else we

are swamped with oncology investment opportunitiesrdquo

Marc LohrmannManaging Partner

Vesalius Biocapital Partners

Is your company featured in this issuePromote it on your website or in your investor kit

For photocopy rights or reprints please contact Adam Lubas at (929) 246-3800 or by email at AdamLubasClarivatecom



Frontierrsquos CEO and president told BioWorldThe South San Francisco-based company is still two years away from clinical development he said and the general targets are cancers and neurodegenerative diseases The American Cancer Society estimates that about 17 million new cancer cases and more than 600000 deaths can be expected just in 2019The fundraising was led by Deerfield Management Droia Oncology Ventures and MPM Capital with participation from DCVC Bi RA Capital Management and others The funding will enable Frontier to invest in research and development talent acquisition and to advance its platform and therapeutic programs

ldquoThe funding gets us into the clinicrdquo Varma said ldquoItrsquos three-plus years of capitalrdquoVarma was a venture partner at MPM Capital He also co-founded Warp Drive Bio (acquired by Revolution Medicines in 2018) while at Third Rock Ventures Prior to that he was partner at Flagship Pioneering focusing on life sciences investments Before joining Flagship he oversaw efforts spanning business development strategy and sales and marketing at Novartis AG He has a

PhD in biomedical sciences from the Harvard-MIT Program in Health Sciences amp Technology a masterrsquos in management from Stanford University and bachelorrsquos and masterrsquos degrees in computer science from Stanford Frontier uses chemoproteomics as its platform to discover and target new binding pockets on proteins making them accessible to small-molecule drug discovery and development Those proteins that were inaccessible for therapeutic intervention were the previously classified ldquoundruggablerdquo keys to developmentldquoDrugging the undruggable proteins that are known to cause cancer and other diseasesrdquo Varma said ldquoWe believe that this is the fastest way to make an impactrdquo There are 20000 human proteins and Varma said science has for the past 100 years been going after only about 10 of them Itrsquos that other 90 that interests Varma as it does other biopharmaceutical companies that are on the same hunt such as Kymera Inc (See BioWorld Oct 31 2017)That unknown 90 waiting to be investigated is the frontier that gave the company its nameBy and large to be considered tractable targets need to be either extracellular or have deep pockets somewhere in their structure for small molecules to bind in Other swaths of potential targets ndash those sometimes called ldquoundruggablerdquo ndash are often ignored (See BioWorld May 29 2012)ldquoOur platform currently includes a database of hotspots that cover a majority of human proteins including those that were previously considered lsquoundruggablersquo an expanding library

of diverse covalent compounds being driven by machine learning and a novel approach to protein degradationrdquo said Daniel K Nomura who along with Varma is a co-founder of Frontier ldquoThis platform enables us to go after almost any protein target of interest for therapeutic interventionrdquoNomura an associate professor of molecular and cell biology chemistry nutritional science and toxicology at UC Berkeley ran the Nomura Research Group for more than eight years a company that focused on investigating previously undruggable proteins using chemoproteomics platforms to develop new disease therapies Frontierrsquos third co-founder is Roberto Zoncu assistant professor of molecular and cell biology at UC Berkeley Zoncu focuses on fundamental mechanisms of growth regulation in both normal and cancer states His work has been recognized by numerous awards including the NIH Director New Innovator Award the Pew Stewart Scholarship for Cancer Research the Edward Mallinckrodt Jr Foundation Scholarship and the Damon Runyon-Rachleff Innovation AwardThe chemoproteomics platform also integrates advanced computational approaches and machine learning in drug discovery ldquoChemoproteomics knows where the pockets on the proteins arerdquo Varma said ldquoWe can then screen a compound against a pocket Wersquore using machine learning also so we have a better chance of successrdquoVarma used machine learning previously at Blueprint Medicines Corp where he was co-founder and CEO Hersquos used that experience at Frontier to create a database of binding hotspots that cover the majority of human proteins along with a library of chemically diverse compounds The more diverse the chemistry Varma said the greater the chances of finding high-quality compounds for a hotspot ldquoAt Blueprint Medicines we applied machine learning in library-building approachesrdquo Varma said ldquoThe algorithms have gotten better and we can now do things more quickly and robustlyrdquoMachine learning needs to be used selectively he said so determining how and where it is applied is key to getting the best resultsPartnering could be part of Frontierrsquos future Varma added In the meantime the company wants to aggressively grow its current staff of 10 to 20-plus by the end of this year s

FrontierContinued from page 1

Chris Varma CEO and president Frontier

Advertise hereReach high-level biotechnology professionals every week

For advertising opportunities in BioWorld please contact Adam Lubas at (929) 246-3800 or by email at AdamLubasClarivatecom

Wednesday June 26 2019 BioWorld 0 of 15


Executive Women in Bio (EWIB) a Women in Bio committee is partnering with the Biotechnology Innovation Organization (BIO) to promote gender diversity on corporate boards in the life sciences sector at a time when less than 15 of board positions in the sector are filled by women Through the partnership senior women executives completing EWIBrsquos Boardroom Ready program can choose to be listed on BIO Boardlist a searchable directory of eligible executives BIO launched the directory to accelerate gender racial ethnic and LGBTQ representation on biotech company boards ldquoIt makes more than just common sense but also business sense that governing boards of biopharmaceutical companies reflect the diversity seen within the ranks of their scientists entrepreneurs investors and patientsrdquo said Halozyme Therapeutics Inc President and CEO Helen Torley who chairs BIOrsquos Workforce Development Diversity amp Inclusion Committee The partnership comes just six months ahead of a California deadline for all publicly held corporations headquartered in the state to have at least one woman on their board Companies that fail to do so will face an initial penalty of $100000 with the fine tripling to $300000 for subsequent violations Under California SB 826 which was signed into law last October companies with boards of five directors will be required to have at least two female members by the end of 2021 while those with six or more directors will be required to have at least three women on their board While the law could face legal challenges investor pressure is growing for greater board inclusivity Several countries in Europe have imposed national quotas for female board members and Norway has required corporate boards to be at least 40 female for more than a decade (See BioWorld Oct 4 2018)The FDA will hold a public meeting July 12 to get comments

Regulatory front on a draft guidance on the use of a limited population pathway for antibacterial and antifungal drugs (LPAD) The guidance released a year ago is intended to help sponsors develop labeling for drugs approved under the LPAD path which was made possible by the 21st Century Cures Act In reviewing an application submitted under the LPAD the FDA considers the severity rarity or prevalence of the infection that the drug is intended to treat as well as the availability or lack of alternative treatment in the limited populationThe UKrsquos National Institute for Health and Care Excellence (NICE) opened a consultation on extending the use of real world data to help inform the independent committees that produce its guidance NICE already uses a range of published scientific evidence for its guidance on health technologies and its advisory guidelines demonstrating best practices for diagnosing and managing various conditions It is proposing to expand its use of data to include hospital records of operations registries that collect data on how particular treatments are used surveys of people using services and data collected on national trends such as how many people have a particular condition The consultation is open until Sept 13Australiarsquos Therapeutic Goods Administration (TGA) revised its regulatory guidelines for biologicals to clarify the exclusion criteria for autologous human cells and tissues (HCT) The TGA said it bases its level of regulation of HCT products on the risk to the public associated with a productrsquos manufacturing processes and intended use It also considers whether there is sufficient regulation by other bodies to mitigate the risks Under the current guidelines the agency will not regulate HCT products when the cells or tissues are collected from a patient under the care of a registered medical or dental practitioner and the HCT is manufactured by that practitioner or someone under his or her supervision in a hospital where the consumer is a patient The HCT product cannot be directly advertised to consumers



Other news to note

Actinium Pharmaceuticals Inc of New York said at the Society of Nuclear Medicine and Molecular Imaging meeting in Anaheim Calif that effective lymphodepletion with the radioisotope Lu-177 or lutetium-177 was achieved with its adoptive cell therapy program for achieving safe effective and transient lymphodepletion prior to the administration of CAR T and other adoptive cell therapies The antibody radiation-conjugates used in the ACT program combines a CD45-targeting antibody with the cell-killing power of radioisotopes Actinium is developing its ACT program to be a potential replacement of nonspecific chemotherapy-based lymphodepletionAlmirall SA of Barcelona Spain and Dermira Inc of Menlo Park Calif said Almirall has exercised its option to license rights to develop and commercialize lebrikizumab for the treatment of atopic dermatitis and certain other indications in Europe Almirall and Dermira previously entered an option and license agreement in February 2019 pursuant to which Almirall was granted that exclusive option in exchange for an up-front option fee of $30 million As a result of Almirallrsquos decision to exercise its option the company will pay Dermira $50 million and Dermira will be eligible to receive additional payments upon the achievement of certain milestones including $30 million in connection with the initiation of certain phase III studies Lebrikizumab is an injectable humanized monoclonal antibody designed to bind interleukin-13Axim Biotechnologies Inc of New York said products from its oral care line including its cannabinoid-based mouthwash and toothpaste were included in registration for clinical trials through the Australian and New Zealand Clinical Trial Registry The trials were registered by Impression Healthcare Ltd of Melbourne Australia a home dental impression company which plans to conduct a phase IIa randomized controlled trial to evaluate the safety and efficacy of the products in 40 people suffering from gingivitis and gum disease Trial participants will use the toothpaste and mouthwash three times a day over 30 days and will be monitored for gum inflammation and overall gum healthBound Therapeutics LLC of Marlton NJ said the National Cancer Institute has awarded the company a Small Business Technology Transfer grant for $300000 to develop a treatment focused on microRNA-21 blockade of triple-negative breast cancer The company said its technology promises greater potency and greater gene specificity because the design platform yields shorter microRNA blockers than standard approaches The design platform uses a next-generation RNA analogue with drug-like properties that efficiently destroys target cancer-related microRNAs at a low dose with negligible toxicity for normal cells negligible immune reactions and negligible gene disruption Bound saidC4X Discovery Holdings plc (C4XD) of Manchester UK said it agreed to collaborate with Phoremost Ltd of Cambridge UK to pursue drug discovery targets in neurodegeneration initially in Parkinsonrsquos disease (PD) Phoremostrsquos Siteseeker screening platform will be used in conjunction with C4XDrsquos target identification platform Taxonomy3 to provide chemical starting

points for drug discovery programs and to bolster C4XDrsquos drug discovery pipeline C4XD expects to advance several PD targets to multitarget disease area partnering arrangements or in-house discovery programs The collaboration may potentially be expanded to additional indications Financial terms were not disclosed but the companies said they expect to share revenues on validated targets produced by the collaborationConatus Pharmaceuticals Inc of San Diego engaged Oppenheimer amp Co Inc as its financial advisor to assist in the exploration and evaluation of strategic alternatives Conatus also is implementing a restructuring plan that includes reducing staff by about 40 and suspending development of its inflammasome disease candidate CTS-2090 The company has updated its financial guidance and is projecting a year-end 2019 net balance of cash cash equivalents and marketable securities of between $10 million and $15 million Shares of the company (NASDAQCNAT) closed Tuesday at 29 cents down 63 cents or 69Generex Biotechnology Corp of Miramar Fla said it signed a letter of intent to merge with Kiromic LLC of Lubbock Texas in an all-stock transaction into newly formed Nugenerex Immuno-Oncology which will house Kiromic and the Generex subsidiary Antigen Express Inc which is developing AE-37 in combination with checkpoint inhibitors to treat triple-negative breast cancer Kiromic which collaborates with MD Anderson Cancer Center has immuno-oncology platforms that include CAR T and CAR NK candidates an oral vaccine delivery system and an artificial intelligence (AI) system Diamond AI comprising a predictive algorithm that combines genomic sequencing proteomic analysis and clinical data to identify tumor mutations that can be targeted with immunotherapy Kiromic used the AI technology to identify and validate several cancer biomarkers including BSK-02 (previously sperm protein 17) which was granted FDA orphan drug designation for ovarian cancer and is in early stage trials in an injectable formulation Additional merger terms were not disclosedGilead Sciences Inc of Foster City Calif and Carna Biosciences Inc of Kobe Japan said they agreed to an RampD collaboration focused on development and commercialization of small-molecule compounds in immuno-oncology Gilead will license from Carna global rights to develop and commercialize inhibitors against an undisclosed immuno-oncology target in exchange for an up-front payment of $20 million to Carna which is eligible to receive up to $450 million in additional development and commercial milestone payments plus royalties on net sales As part of the deal Gilead also gained exclusive access to Carnarsquos lipid kinase drug discovery platformHalozyme Therapeutics Inc of San Diego said it formed a Cooperative Research and Development Agreement or CRADA enabling the National Institute of Allergy and Infectious Diseasesrsquo Vaccine Research Center (VRC) to use the companyrsquos Enhanze drug delivery technology to develop subcutaneous formulations of broadly neutralizing antibodies (bnAbs) against HIV to pursue treatments for the disease The VRC will engage in early stage studies in healthy adults to investigate the safety tolerability dose and pharmacokinetics of formulating two bnAbs selected for the CRADA VRC07-523LS and N6LS with Enhanze to optimize subcutaneous administration



III program and has initiated dialogue with the EMA and FDA while actively seeking development partners

QR Pharma Inc of Berwyn Pa said it rebranded as Annovis Bio Inc to better reflect its technology designed to inhibit amyloid precursor protein or APP and to normalize axonal flow in neurodegenerative diseases The company is pursuing therapies to treat Alzheimerrsquos Parkinsonrsquos and other neurodegenerative diseases

Rafael Pharmaceuticals Inc (formerly Cornerstone Pharmaceuticals Inc) of Cranbury NJ said it inked an out-licensing agreement with Ono Pharmaceutical Co Ltd of Osaka Japan to develop and commercialize lead candidate CPI-613 (devimistat) in Japan and other countries in Asia Rafael is set to receive an up-front payment of approximately $129 million and up to approximately $1503 million in potential development and commercial milestone payments as well as low-double digit royalties on net sales in Japan South Korea Taiwan and Association of Southeast Asian Nations or ASEAN countries Ono gained exclusive rights to develop and commercialize the candidate for all indications in its territory while Rafael retained all rights elsewhere A pyruvate dehydrogenase inhibitor CPI-613 is in multiple phase III studies in cancer indications (See BioWorld Dec 12 2018)

Taiwan Liposome Co Ltd (TLC) of Taiwan said it signed a development and license agreement with Birdie Biopharmaceuticals Inc a wholly owned subsidiary of Seven and Eight Biopharmaceuticals Inc of Edison NJ to advance a liposomal formulated dual agonist candidate against Toll-like receptors 7 and 8 (TLR78) using TLCrsquos Nanox technology Birdie will oversee preclinical and clinical development regulatory filings and commercialization TLC will handle formulation development and manufacturing in return for an undisclosed up-front payment and up to $49 million in potential milestone payments plus royalties on net sales Additional terms were not disclosed Last week Seven and Eight disclosed a research collaboration with Roche Holding AG of Basel Switzerland to explore the combination of BDB-001 an immune modulator targeting TLR78 and atezolizumab (Tecentriq) in solid tumors (See BioWorld June 21 2019)

Theralase Technologies Inc of Toronto said a scientific paper pertaining to its Rutherrin-based photodynamic therapy (PDT) was selected for publication in Neuro-Oncology Advances Theralase said the findings highlighted two aspects of the PDT to target brain tumor gliomas including the ability to cross the blood-brain barrier through an active transport mechanism The paper also showed that Theralase PDC can be activated with longer wavelengths of laser light in the near infrared optical spectrum to enable precise insertion of optical fibers into the tumor to treat larger tissue volumes

Tilt Biotherapeutics Ltd of Helsinki Finland said it inked an agreement with Merck KGaA of Darmstadt Germany and Pfizer Inc of New York to evaluate its armed oncolytic virus TILT-123 with avelumab (Bavencio) in solid tumors refractory to routine modalities Financial terms were not disclosed

Intensity Therapeutics Inc of Westport Conn said it inked an agreement with Merck amp Co Inc of Kenilworth NJ to evaluate the combination of Intensityrsquos lead candidate INT-230-6 with Keytruda (pembrolizumab) in individuals with advanced solid malignancies including pancreatic bile duct squamous cell and non-microsatellite instability high colon cancers The combination portion of Intensityrsquos phase III program with INT-230-6 a combination of cisplatin and vinblastine with an amphiphilic penetration-enhancement excipient is expected to begin in the second half of the year Karo Pharma AB of Stockholm acquired all the shares of Trimb Holding AB also of Stockholm for about $366 million The transaction is subject to regulatory review and anticipated to close before the end of 2019 Trimb is a consumer health care company based in Stockholm with approximately 90 employees The firm owns licenses to markets and sells a large number of over-the-counter pharmaceuticals and consumer health care products

Lixte Biotechnology Holdings Inc of East Setauket NY said neuroscientists in China and Japan working independently of the company reported in Proceedings of the National Academy of Sciences that its lead compound LB-100 improved muscle strength movement coordination and learning in a mouse model of Angelman syndrome (AS) Mice genetically modified to have reduced function of the UBE3A gene have features of human AS including movement disorder seizure phenomena and cognitive impairment as well as abnormalities in structural features of brain cells In their publication researchers said they found that brain tissue of AS mice showed increased concentrations of protein phosphatase 2A (PP2A) a molecular target of LB-100 Systemic administration of the PP2A inhibitor to young AS mice improved their movement disorder and the structure and function of abnormal brain cells The findings also indicated that some LB-100 penetrated the brain of mice with AS

Medidata Solutions Inc of New York said Orion Oyj of Espoo Finland plans to consolidate its clinical trials on the Medidata Rave Clinical Cloud and to expand its use of trial management solutions to support growth of its RampD pipeline Financial terms were not disclosed

Oxford Biotherapeutics Ltd of Oxford UK said it received a milestone payment from Boehringer Ingelheim GmbH (BI) of Ingelheim Germany related to advancement of a BI candidate in an immuno-oncology program enabled through Oxfordrsquos Oxford Genome Anatomy Project or OGAP target discovery platform To date BI has exercised two options under the 2013 agreement according to Oxford Premark Pharma GmbH of Basel Switzerland said it concluded a licensing deal with Novartis AG also of Basel to gain exclusive global rights to develop and commercialize PMP-2207 which it described as an ophthalmic ointment formulation of an established anti-inflammatory to treat blepharitis an inflammation of the eyelid Premark said it plans to move the agent into a phase

Other news to note



Clinical data for June 25 2019

Company Product Description Indication Status

Phase I

I-Mab Biopharma Co Ltd of Gaithersburg Md and Shanghai

TJC-4 CD47 antagonistHematological neoplasm solid tumor

First patient dosed in study to evaluate the safety tolerability pharmacokinetics pharmacodynamics and preliminary efficacy in advanced solid tumors and lymphoma when administered as a single agent and in combination with other cancer treatments

Imbrium Therapeutics LP of Stamford Conn

IMB-115 (previously IT-1315)

Undisclosed

Healthy volunteers (eventually insomnia associated with alcohol cessation)

A study of the drugs abuse potential in 50 recreational sedative users showed drug liking of the 1-mg dose wasnt statistically different from placebo supratherapeutic doses of IMB-115 (6 mg and 10 mg) showed drug liking and adverse events that were similar to the positive control (triazolam 05 mg and 1 mg) no amnestic effects were noted with IMB-115 in a separate alcohol-interaction study in 48 subjects there were no significant changes in pharmacokinetic parameters when IMB-115 (2-mg or 6-mg doses) were taken with alcohol there were no significant changes in clinical laboratory values vital signs or oxygen saturation levels

Rodin Therapeutics Inc of Cambridge Mass

RDN-929 HDAC-CoREST inhibitor

Healthy volunteers (eventually neurologic diseases)

In a study testing single ascending and multiple ascending doses of RDN-929 the drug was deemed safe and well-tolerated with favorable pharmacokinetic and pharmacodynamic properties drug concentrations in cerebrospinal fluid were in the range predicted to be required for efficacy there was a dose-dependent increase across multiple acetylation marks

Phase II

Anavex Life Sciences Corp of New York

ANAVEX2-73-RS-001

Activates Sigma-1 receptor Rett syndrome

First patient enrolled in the 12-week extension study to test the long-term safety tolerability and efficacy in patients who completed the initial 7-week study

Biopharmx Corp of San Jose Calif BPX-04 Solubilized

minocycline

Moderate to severe papulopustular rosacea

In the 208-patient phase IIb study BPX-04 reduced the mean number of facial inflammatory lesions from baseline to week 12 by 136 compared to a mean reduction of 103 lesions for vehicle (p=00040) 523 of patients taking BPX-04 had a 2-grade improvement in Investigators Global Assessment to 0 or 1 from baseline to week 12 compared to 323 of patients using vehicle (p=00180)

Conatus Pharmaceuticals Inc of San Diego and Novartis AG of Basel Switzerland

Emricasan Inhibits caspases

Decompensated nonalcoholic steatohepatitis cirrhosis

The 217-patient phase IIb Encore-Lf study didnt meet its primary endpoint of improving event-free survival defined as a composite of all-cause mortality new decompensation events or ge4 points progression in Model for End-stage Liver Disease score companies are discontinuing the study and the Encore-Ph extension study which did not meet predefined objectives

Diasome Pharmaceuticals Inc of Cleveland

Hepatocyte directed vesicle

Nanoscale frisbee-shaped carrier of insulin molecules

Insulin-dependent diabetes

Completed enrollment in OPTI-1 study of injectable HDV plus insulin 61 patients enrolled at 8 US sites

Dompeacute Farmaceutici SpA of Milan

RhNGF eye solution

Recombinant human nerve growth factor

Severe dry eye disease

Enrolled first of 300 patients in the phase IIb NGF0118 study testing the drug for 4 weeks followed by 12 weeks of observation primary endpoint is the change from baseline in ocular surface tear wetting measured via Schirmer I test signs and symptoms of DED including ocular surface staining will be measured as secondary endpoints

Epicentrx Inc of La Jolla Calif RRx-001

Tumor associated macrophage repolarizing agent

Third-line small-cell lung cancer

Data from 26 patients published in the British Journal of Cancer showed RRx-001 and a platinum doublet produced overall survival of 86 months and progression-free survival of 75 months

Iliad Biotechnologies LLC of Weston Fla

BPZE-1Live attenuated intranasal pertussis vaccine

Bordetella pertussis infection

First subject was enrolled in IB-200P study 300 subjects will be randomly assigned 2-to-1 for the primary vaccination with 200 subjects assigned to BPZE-1 vaccination and 100 subjects to Boostrix primary immunogenicity outcome is the proportion of subjects who achieve seroconversion against at least 1 pertussis antigen in nasal secretions on day 29 or 113 (prime or prime + boost)



UndisclosedInsomnia associated with alcohol cessation

Started study which will begin enrolling patients in July




Immutep Ltd of Sydney

Eftilagimod alpha (IMP-321)

LAG-3Ig fusion protein

HER2-negativeHR-positive metastatic breast cancer

Completed enrollment of study testing drug plus paclitaxel with progression-free survival as the primary endpoint PFS and overall response rate data expected in the first quarter of 2020

Intec Pharma Ltd of Jerusalem AP-CDLD

Carbidopa and levodopa delivered via the Accordion Pill drug release platform

Parkinsons disease

Data from cohorts 1-4 published in Parkinsonism and Related Disorders showed levodopa Cmax decreased by 571 and 668 among fluctuating and non-fluctuating patients respectively compared to immediate-release-CDLD treatment with AP-CDLD 50375 twice daily and AP-CDLD 50500 twice daily reduced mean daily OFF time by 44 and 45 compared to immediate-release-CDLD (plt0001 for both)

Oasmia Pharmaceutical AB of Uppsala Sweden

Docecal

Nanoparticle formulation of docetaxel free of ethanol and polysorbate

Metastatic breast cancer

In the 200-patient study noninferiority between Docecal and Taxotere (docetaxel ) for best overall objective tumor response couldnt be determined in patients who completed all 6 cycles Docecal met noninferiority compared to Taxotere

Progenics Pharmaceuticals Inc of New York

PyL PSMA-targeted imaging agent

High-risk and metastatic prostate cancer

In the phase IIIII Osprey study sensitivity and positive predictive value were high in detecting lesions in the pelvic and extra-pelvic regions in men with metastatic disease in an investigator-sponsored study the agent localized to the disease in a large proportion of patients including in men with very low PSA levels in patients with negative conventional imaging positive signal by PyL changed clinical practice in a third study PyL imaging was similar to 18F NaF PETCT in detecting bone metastases

Sound Pharmaceuticals Inc of Seattle

SPI-1005

Induces glutathione peroxidase activity

Menieres disease

After 8 weeks of treatment response rate for improved hearing loss (ge10 dB gain from baseline at 1 low frequency) was 61 for SPI-1005 compared to 37 for placebo (plt0023) word recognition improvement (ge10 increase in word recognition from baseline) response rate was 75 for SPI-1005 compared to 56 for placebo (plt0060)

Phase III

Aldeyra Therapeutics Inc of Lexington Mass

Reproxalap Aldehyde-binding small molecule

Noninfectious anterior uveitis

In the Solace study activity of reproxalap was consistently greater than that of vehicle but study didnt meet the primary or secondary endpoints due to high rates of disease resolution in vehicle-treated patients company plans to focus on ocular programs in dry eye disease allergic conjunctivitis and proliferative vitreoretinopathy

Eisai Inc of Woodcliff Lake NJ

Fycompa (perampanel)

AMPA glutamate receptor antagonist Partial seizure

In a single-arm study 63 of patients ge12 years with newly diagnosed or untreated epilepsy treated with 4 mgday achieved seizure freedom at 26 weeks

Poxel SA of Lyon France and Sumitomo Dainippon Pharma Co Ltd of Osaka Japan

ImegliminAMP activated protein kinase stimulator

Non-insulin-dependent diabetes

Reported imeglimin in combination with insulin met its primary endpoint of change of glycated HbA1c from baseline vs placebo at week 16 with a mean HbA1c placebo-corrected change from baseline of -060 with a favorable safety and tolerability profile in TIMES 3 trial

NotesFor more information about individual companies andor products see Cortellis

Regulatory actions for June 25 2019


Abbvie Inc of North Chicago

Venclexta (venetoclax)

Bcl-2 protein inhibitor

Chronic lymphocytic leukemia

Quebecs Institut national dexcellence en santeacute et en services sociaux recommended reimbursement of Venclexta in combination with rituximab for the treatment of adult patients with CLL

Acer Therapeutics Inc of Newton Mass

Edsivo (celiprolol) Beta-blocker Ehlers-Danlos

syndrome

FDA issued a CRL calling for the company to conduct an adequate and well-controlled trial to determine whether the orphan-designated drug reduces the risk of clinical events in patients with vascular EDS

Agile Therapeutics Inc of Princeton NJ

Twirla (AG200-15)

Low-dose levonorgestrelethinyl estradiol transdermal contraceptive patch

Female contraception

Meeting of FDAs Bone Reproductive and Urologic Drugs Advisory Committee scheduled for Oct 30 2019 to review NDA after company resubmitted application in May PDUFA date is Nov 16




Arvinas Inc of New Haven Conn ARV-471

Oral estrogen receptor PROTAC protein degrader

Breast cancer Company expects to initiate phase I trial in Q3 2019

Dova Pharmaceuticals Inc of Durham NC

Doptelet (avatrom-bopag)

Thrombopoietin receptor agonist

Severe thrombocytopenia

European Commission granted approval for use in adults with chronic liver disease who are scheduled to undergo an invasive procedure

Ipsen SA of ParisSomatuline Depot (lanreotide)

Somatostatin analogue

Gastroentero-pancreatic neuroendocrine tumors carcinoid syndrome acromegaly

FDA approved new prefilled syringe designed for easier administration for same indications as previously approved prefilled syringe

Nabriva Therapeutics plc of Dublin

LefamulinSemisynthetic pleuromutilin antibiotic

Community-acquired pneumonia

EMA determined MAA was valid formal review process to begin with opinion from Committee for Medicinal Products for Human Use anticipated in next 12 to 15 months

Santhera Pharmaceuticals AG of Pratteln Switzerland

Puldysa (idebenone)

Synthetic short-chain benzoquinone and co-factor for enzyme NAD(P)Hquinone oxidoreductase

Respiratory dysfunction in Duchenne muscular dystrophy patients

EMA validated MAA for formal review opinion expected by Committee for Medicinal Products for Human Use around mid-2020


Looking for the next blockbuster drugNovel targets are the key to success

With the primary reason for phase 2 and phase 3 clinical trial failures being due to a drugrsquos lack of efficacy properly identifying novel targets for drug development is the key to improving your chance of developing a first-in-class or best-in-class drug

To learn more visit InfoclarivatecomTarget_ID_Article

Wednesday June 26 2019 BioWorld of 15

BioWorldBioWorld (ISSN 1541-0595) is published every business day by Clarivate Analytics

Opinions expressed are not necessarily those of this publication Mention of products or services does not constitute endorsement

copy 2019 Clarivate Analytics All rights reserved Republication or redistribution of Clarivate Analytics content including by framing or similar means is prohibited without the prior written consent of Clarivate Analytics Clarivate and its logo are trademarks of the Clarivate Analytics group

Our newsroom Lynn Yoffee (News Director) Jennifer Boggs (Managing Editor) Peter Winter (BioWorld Insight Editor) Michael Fitzhugh (News Editor) Anette Breindl (Senior Science Editor) Mari Serebrov (Regulatory Editor) Amanda Lanier (Managing Editor) Karen Pihl-Carey (Analyst) Ann Marie Griffith (Production Editor)

Staff writers Randy Osborne Shannon Ellis John Fox Nuala Moran Brian Orelli Alfred Romann Tamra Sami Cormac Sheridan

Practical informationFor sales inquiries httpsclarivatecomproductsbioworld In North America call 1-855-260-5607 Outside of the US and Canada call +44-203-684-1797

For customer service support httpssupportclarivatecomLifeSciences In North America call 1-800-336-4474 Outside of the US and Canada call +44-203-684-1796

For ad rates and information contact Adam Lubas at (929) 246-3800 or email AdamLubasClarivatecom

For photocopy rights or reprints contact Adam Lubas at (929) 246-3800 or email AdamLubasClarivatecom

Send all press releases and related information to newsdeskbioworldcom

Business office John Borgman (Director of Commercial Competitive Intelligence) Donald Johnston (Senior Marketing Communication Director Life Sciences)

Contact usJennifer Boggs (770) 880-3631 | John Borgman (831) 462 2510 | Anette Breindl (770) 810-3134 | Michael Fitzhugh (770) 810-3064 | Donald Johnston (678) 641-0970 | Nuala Moran 44-7778-868-579 | Randy Osborne (770) 810-3139 | Mari Serebrov (770) 810-3141 | Cormac Sheridan 353-87-6864323 | Peter Winter (770) 810-3142 | Lynn Yoffee (434) 964-4011

Financings

Akero Therapeutics Inc of San Francisco said it closed its IPO of 66 million shares including the exercise in full by the underwriters of their option to purchase up to 862500 additional shares at $16 each for aggregate gross proceeds of approximately $1058 million The companyrsquos common stock is listed on Nasdaq under the ticker symbol AKROArqule Inc of Burlington Mass said it priced an underwritten public offering of 925 million shares at $975 each The underwriters have been granted a 30-day option to purchase up to an additional 138 million shares of its common stock The gross proceeds excluding any exercise by the underwriters of their option are expected to be approximately $902 million and it intends to use net proceeds to fund clinical programs and for general corporate purposesArtelo Biosciences Inc a La Jolla Calif-based company developing medicines targeting the endocannabinoid system announced the closing of its previously announced underwritten public offering of about 13 million units at $615 per unit Each unit consisted of one share of common stock (NASDAQARTL) and one warrant to purchase one share of common stock at an exercise price of $646 per share The company received gross proceeds of $8 million In connection with the offering it conducted a reverse split of its common stock at a ratio of 1-for-8 Company shares fell 33 cents Tuesday to close at $460Eloxx Pharmaceuticals Inc of Waltham Mass said it closed its underwritten public offering of 383 million shares of its common stock which includes the full exercise of the underwritersrsquo option to purchase an additional 500000 shares at $9 per share The gross proceeds were approximately $345 million and the net proceeds will be used to fund the continued clinical development of ELX-02 in cystic fibrosis and cystinosis to accelerate development of early stage programs and for working

capital and other general corporate purposesGamida Cell Ltd of Boston said it is planning a proposed follow-on public offering of approximately $30 million of its ordinary shares In addition the underwriters will be granted a 30-day option to purchase up to $45 million of additional ordinary sharesKrystal Biotech Inc of Pittsburgh said it priced an underwritten public offering of 25 million shares of its common stock at $40 each and the underwriters have been granted a 30-day option to purchase up to an additional 375000 shares The gross proceeds are expected to be approximately $100 millionMirati Therapeutics Inc of San Diego said it intends to offer and sell subject to market and other conditions $75 million of shares of its common stock in an underwritten public offering The company expects to grant the underwriters a 30-day option to purchase up to an additional $1125 million of shares of its common stockSareum Holdings plc of Cambridge UK raised gross proceeds of pound513200 (US$651400) through a placement by Hybridan LLP of 1283 million new ordinary shares (AIMSAR) of 0025 pence each in the capital of the company at 04 pence per share It said net proceeds will be used to advance the companyrsquos preclinical TYK2JAK1 assets SDC-1801 and SDC-1802 as well as for working capital purposes Tetra Bio-Pharma Inc of Ottawa Ontario said it priced its marketed public offering of units at a CA30 cents (US23 cents) per unit which will consist of one common share and one common share purchase warrant that will entitle its holder to acquire one common share at an exercise price of CA40 centsThe Medicines Co of Parsippany NJ said it launched a public offering of $150 million of shares of its common stock In addition the underwriters will be granted a 30-day option to purchase up to an additional $225 million of shares of common stock The company expects to use the net proceeds to fund its development of inclisiran a cholesterol-lowering GalNAc-conjugated RNA interference therapeutic and for general corporate purposes







See Abbvie page 4









Regulatory front




















Regulatory front








Regulatory front



























Other news to note















Other news to note





Phase I






Undisclosed







Phase II


ANAVEX2-73-RS-001




minocycline













RhNGF eye solution


























Parkinsons disease



Docecal









SPI-1005


Menieres disease


Phase III























syndrome



Twirla (AG200-15)
























Puldysa (idebenone)














See Abbvie page 4









Regulatory front




















Regulatory front








Regulatory front



























Other news to note















Other news to note





Phase I






Undisclosed







Phase II


ANAVEX2-73-RS-001




minocycline













RhNGF eye solution


























Parkinsons disease



Docecal









SPI-1005


Menieres disease


Phase III























syndrome



Twirla (AG200-15)
























Puldysa (idebenone)
















Regulatory front




















Regulatory front








Regulatory front



























Other news to note















Other news to note





Phase I






Undisclosed







Phase II


ANAVEX2-73-RS-001




minocycline













RhNGF eye solution


























Parkinsons disease



Docecal









SPI-1005


Menieres disease


Phase III























syndrome



Twirla (AG200-15)
























Puldysa (idebenone)



























Regulatory front








Regulatory front



























Other news to note















Other news to note





Phase I






Undisclosed







Phase II


ANAVEX2-73-RS-001




minocycline













RhNGF eye solution


























Parkinsons disease



Docecal









SPI-1005


Menieres disease


Phase III























syndrome



Twirla (AG200-15)
























Puldysa (idebenone)














Regulatory front



























Other news to note















Other news to note





Phase I






Undisclosed







Phase II


ANAVEX2-73-RS-001




minocycline













RhNGF eye solution


























Parkinsons disease



Docecal









SPI-1005


Menieres disease


Phase III























syndrome



Twirla (AG200-15)
























Puldysa (idebenone)


































Other news to note















Other news to note





Phase I






Undisclosed







Phase II


ANAVEX2-73-RS-001




minocycline













RhNGF eye solution


























Parkinsons disease



Docecal









SPI-1005


Menieres disease


Phase III























syndrome



Twirla (AG200-15)
























Puldysa (idebenone)




















Other news to note





Phase I






Undisclosed







Phase II


ANAVEX2-73-RS-001




minocycline













RhNGF eye solution


























Parkinsons disease



Docecal









SPI-1005


Menieres disease


Phase III























syndrome



Twirla (AG200-15)
























Puldysa (idebenone)












Phase I






Undisclosed







Phase II


ANAVEX2-73-RS-001




minocycline













RhNGF eye solution


























Parkinsons disease



Docecal









SPI-1005


Menieres disease


Phase III























syndrome



Twirla (AG200-15)
























Puldysa (idebenone)


















Parkinsons disease



Docecal









SPI-1005


Menieres disease


Phase III























syndrome



Twirla (AG200-15)
























Puldysa (idebenone)




























Puldysa (idebenone)








bioworld - frontiermeds.com, of boston, said it is planning a proposed follow-on public offering of...

Documents