AWARD LETTER AGREEMENT

THIS AGREEMENT made on this 29th day of December 2015, between SRISTI,Society for Research and Initiatives for Sustainable Technologies and Institutions(hereinafter called as SRISTI), a non-profit organization having its office at AES BoysHostel Campus, Near Gujarat University Library & SBI, Navrangpura, Ahmedabad-380009, Gujarat, India; of the ONE PART and Venkateswarlu Yarlagadda student ofIawaharlal Nehru Centre for Advanced Scientific Research (INCASR) (Institute/University)hereinafter called AWARDEE of the OTHER PART:

Whereas, SRISTI is an organization set up with the objective of strengthening thecapacity of grassroots and student, inventors, innovators and ecopreneurs in the areaof conserving biodiversity and developing eco-friendly solution to local problems; isengaged inter alia in the area search, documentation, experimentation, development,diffusion of sustainable technologies and Techpedia, a Sristi initiative aims atputting the problems of micro, small and medium enterprises, informal sector,grassroots innovators and other social sectors on the agenda of the young technologystudents across the country.

Whereas to promote the culture of innovation amongst the young minds of thecountry, SRISTI established three national awards for innovative student/ facultyprojects in engineering, pharmacy, science and applied technologies since 2012 in thename of Gandhian Young Technological Innovation Award (GYTI). Realising theneed of the hour and looking at the innovation potential of awardees, BiotechnologyIndustry Research Assistance Council (BIRAC) a Government of India Enterprise ofDepartment of Biotechnology (DBT), New Delhi has decided to give BIRAC-SRISTIGYTI Awards and BIRAC-SRISTI GYTI Appreciation Awards (hereinafter referredto as "Program" jointly or severally) administered through the Project ManagementUnit (PMU-BIRAC- SRISTI) at SRISTI.

WHEREAS Venkateswarlu Yarlagadda R/o , studying/ workingat Iawaharlal Nehru Centre for Advanced Scientific Research (INCASR) (Institute/Universityj has been selected for BIRAC-SRISTI GYTI Award/ BIRAC-SRISTI GYTIAppreciation Award for the research Project entitled "Development of a powerfulnew antibiotic that kills all drug resistant bacteria" , hereinafter referred to asPROJECT and Appended herein as Annexure-I WHEREAS all the Annexures to thisAgreement shall be read as integral part of the Agreement.

AND WHEREAS both SRISTI and the Awardee together shall be referred to asParties.

NOW THEREFORE the Parties on valid consideration and mutual covenants enter into this AWARD LETTER AGREEMENT, hereinafter referred to as “ALA” as provided hereunder:

I. The Awardee will communicate with Coordinator, Project Management Unit (PMU-BIRAC-SRISTI) on pmugyti@sristi.org

II. The Awardee shall undertake the activities as set out in the Project and shall

conform to the detailed plan of work, specified objectives, outputs, milestones, and targets as detailed in Annexure-I.

III. The sanction of the Award fund is subject to due submission of the expected

time period of completion (months), details of expenses under suitable heads, with no objection of Supervisor/Guide along with the bank account details for remitting instalments of award money.

IV. SRISTI will transfer the award fund to the account details provided by the

Awardee. To ensure proper utilization of the fund, it will be necessary to send the utilization certificate yearly and after the completion of the project duly signed by team member as and when required. Team member may not include faculty supervisor.

V. The Awardee will maintain a logbook of activities based upon the standard

good laboratory practice (GLP). A timeline of work plan will also have to be provided in the logbook.

VI. Where ever required the Supervisor/Guide of the awardee will be informed

about the decisions made during the project. Since the team members of the project may vary within a time frame of two years, Supervisor/Guide will ensure to give suitable credits to each contributor during or after the period of the research/project.

VII. The Awardee may induct their colleagues and juniors interested in the project

to take the innovation forward. However, if desired the Supervisor / Guide should be informed before such induction.

VIII. The Awardee will be responsible to ensure that the best ethical practices are

followed during the project implementation.

IX. The Awardee is allowed to take the help (pro-bono or on payment basis) of external agencies/ laboratories/ scientific experts during the course of their research / project support. However, complete outsourcing of work will not be allowed. This should be clearly mentioned in the details of expenses under the head „Outsourcing‟.

X. There will be an online monitoring of the project progress; the Awardee will

be required to upload the progress on regular basis. However, the review of the progress will be on half yearly / yearly basis.

XI. The Awardee will submit a 15-20 page final report about the achievements at

the end of the Project period.

XII. The Awardee should comply with the Institutional IP Policy if required by the institution concerned.

XIII. If any Intellectual Property (IP) is generated during the course of Project (Project IP), it should be duly informed to SRISTI and BIRAC without any delay.

XIV. BIRAC and SRISTI will not seek any financial benefit from the outcome of the

projects in licensing/technology transfer. However, it will be obligatory to acknowledge the BIRAC SRISTI GYTI Award, 2015 in any publications or IP generated from this support.

XV. If the Awardee is applying for licensing of their Project IP, it will be necessary

for them to inform SRISTI.

XVI. The Awardee may apply for funding support to other agencies including BIRAC, under intimation to the Supervisor/Guide, SRISTI and BIRAC.

XVII. If the Awardee has any parallel funding support, or they are in collaboration

with any other funding agency-the terms and conditions of the collaboration will have to be shared clearly with SRISTI before execution of this ALA. The Awardee cannot avail support from two funding agencies for the same task/project at the same time. The BIRAC-SRISTI GYTI Award/Appreciation Award shall have exclusive deliverable though it may be part of a long term research work.

Settlement of disputes: Any difference or dispute between the parties or Awardee & Supervisior/Guide concerning the interpretation and/or implementation and/or application of any of the provisions of this agreement shall first be settled amicably through mutual consultation and/or negotiations between the parties; else President SRISTI/MD BIRAC / CIO-NIF may be invited as an arbitrator. Revision, variation and amendment

Awardee may request in writing a revision, variation or amendment of this agreement. Any such revision, variation or amendment agreed to by the parties shall be in writing and shall form part of this agreement. Such revision, variation or amendment shall come into force on such date as may be determined by the parties.

Annexure I

1. Name of the Innovation /Project: Development of a powerful new antibiotic that kills all drug resistant bacteria

2. Specific Objective of the activities to be supported by BIRAC-SRISTI GYTI

Grant: i. We propose to develop lipophilic cationic vancomycin analogues that

would be active against multidrug-resistant bacteria with less/no

toxicity towards mammalian cells. The final compounds will be

designed to have an optimum hydrophobic/hydrophilic balance,

which will direct their selectivity towards bacterial cells over

mammalian cells. The compounds will exhibit antibacterial activity by

disrupting the bacterial cell membrane.

ii. Specifically, we propose to synthesize vancomycin analogues bearing

an amide bond between the lipophilic hydrocarbon chain and the

quaternary nitrogen atom to reduce the toxicity towards mammalian

cells.

iii. To systematically evaluate their in-vitro efficacy against drug-resistant

bacteria such as MRSA, VISA, VRSA and VRE.

iv. To test their in-vitro and in-vivo toxicity

v. To elucidate their membrane disruption properties.

vi. To evaluate in-vivo antibacterial activity of the optimized compound in

mice.

vii. To study the propensity of resistance development in bacteria to the

new vancomycin analogues.

3. Plan of Work: Activites, Time Periods & Milestones:

Sr. No

Activities

Time Line in Months

Milestone 1-3 4-6 7-9 10-12 13-15 16-18 19-21 22-24

1

i) Synthesis of new modified compounds ii) Testing in-vitro efficacy of above synthesized compounds against drug-resistant bacteria

Synthesis of a variety of vancomycin derivatives with varying chain length and to get the lead molecule by screening them for antibacterial activity.

2

Testing in-vitro efficacy against clinical isolates from patients and resistance study

Lead compound will be identified and possibility of acquiring resistance in bacteria against new compound will be determined.

3

Mechanistic studies and In-vitro toxicology of the lead compound

Membrane disruption properties and other possible mechanistic studies of the new compound will be investigated. Safety of the compounds towards mammalian cells will be evaluated to optimize the compound efficacy.

4

In-vivo toxicity (LD50) and efficacy in mouse infection model (skin infection model)

Safety profile of the lead molecule in lower animals will be determined and the efficacy of the drug will be assessed by obtain at least 3-orders bacterial reduction in mouse model.

Sr. No.

Activities Indicators of success Risk

involved in this step

Specific mentoring or

contact or skill

required

Infrastructure /Lab facility

required

1 Synthesis of new molecules

Synthesis of a variety of vancomycin derivatives with varying chain length and to get the lead molecule.

NA Synthetic

organic chemist

2

Testing of in-vitro activity of the compounds against various wild type and

Antibacterial activity of the new compounds will be determined.

NA

Microbiologist and

Medicinal chemist

drug-resistant bacterial strains

3 Mechanistic studies

Membrane disruption properties and other possible mechanistic studies of the new compounds will be investigated.

NA

Microbiologist and

Medicinal chemist

4 Resistance study

Concentration at which the compound has the propensity to develop resistance would be determined

NA Trained

Veterinary

5 In-vitro and in-vivo toxicity LD50 determination

Safety of the compounds towards mammalian cells will be evaluated to optimize the compound efficacy and LD50 determination

NA Trained

Veterinary

6 In-vivo test of efficacy in mouse skin infection model.

Obtain 3 log reduction in mouse model.

NA Trained

Veterinary

4. Outputs: Bacterial resistance threatens to bring back the pre-antibiotic era when people died of bacterial infections. This calls for an urgent need for development of new antibiotics with new modes of action. If an antibiotic developed in India is commercialized, it would be highly beneficial to the Indian economy as well as the public health. The new antibiotic developed by us kills bacteria through multi-faceted mechanism, which might boost the antibiotic development globally. Also, we will be getting some backup molecules which could be potential candidates for treating drug-resistant bacterial infections.

5. Detail of Expenses:

Head 1-6

months 7-12

months 13-18

months 19-24

months

1. Scholarship 2.81 lacs 2.81 lacs 2.81 lacs 2.81 lacs

2. Consumable & Materials

0.94 lacs

0.94 lacs

0.94 lacs

0.94 lacs

3. Internal Travel NA NA NA NA

4. Outsourcing

NOTE :

1. The expense chart is prepared by taking certain assumptions. The numbers are

approximated in the round figures and the actual expenses might vary from the

projected amounts. The scholarship charges are based on the assumption that a

postdoctoral scientist (will be funded by this project) and a graduate student (funded by

the institute) would be working on the project throughout the span of 24 months. The

scholarship amount is based on the revised fellowship according to Department of

Science and Technology (DST), India.

2. Consumables would include the expenses over various services and raw materials (eg.

starting materials, glass ware, equipments etc.)

6. Bank Details: Name of Account Holder: Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) Account Number: 0683101018520 Name of the Bank: Canara Bank Branch: Indian Institute of Science Branch IFSC code of the Bank: CNRB0000683

7. No objection Certificate (NOC) of Supervisor/Guide: