B. SSJ_signed.pdf

1. Requesting Organization.

a. Name of the Institute or Center National Institute on Drug Abuse (NIDA), Translational Addiction Medicine Branch (TAMB), Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section (CPN)

b. Name of the Office / Division / Branch / Program Office Translational Addiction Medicine Branch (TAMB)

c. Project Officer Information

Lorenzo Leggio, MD, PhD

NIDA IRP

Biomedical Research Center 251 Bayview Boulevard Suite 200, Room 04A515 Baltimore, MD 21224 Phone: (443) 740-2801 Mobile: (240) 478-1503 Email: lorenzo.leggio@nih.gov

2. Project Description.

a. Project Title. Manipulating Ghrelin signaling via GOAT inhibition in alcohol use disorder.

3. Acquisition purpose and objectives.

The National Institute on Drug Abuse Intramural Research Program (NIDA IRP), Translational Addiction Medicine Branch, Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section (TAMB/CPN) conducts addiction-related translational research. A combination of preclinical, animal, and human clinical research is used to develop novel effective addiction treatments and precision medicine approaches. Research focused on identifying feeding-related pathways may be of utility in understanding the neurobiology of alcoholism and may yield possible neuropharmacological targets for alcohol use disorder.

TAMB/CPN requires the continuance of the proof of concept for a human laboratory study testing the potential early signal of efficacy of GLWL-01 in relation to alcohol related behavior. The certification for this investigational drug is set to expire on August 26, 2022. It is imperative that stability testing on this study, GLWL-01, be completed by August 26, 2022, to recertify and extend its use and expiration date. This would allow the study to proceed uninterrupted, preserve the safety of active participants, and the integrity of the research.

Sole/Single Source Justification for Requirements Exceeding $10,000, but not Exceeding $250,000 mailto:lorenzo.leggio@nih.gov

Project background

Alcohol use disorder (AUD) is a chronic relapsing brain disease that results in severe consequences including serious morbidity and mortality (NIAAA,2018). According to recent data, approximately 30% of the US adult population meets criteria for lifetime diagnosis of AUD (Grant et al., 2015; Miller & Cohen, 2001). Treatment of AUD consists of psychological, social and pharmacologic interventions (Garbutt, West, Carey, Lohr, & Crews, 1999). When combined with psychosocial treatments, medications can improve outcomes for some individuals; however, these treatments are not effective for many others (Edwards, Kenna, Swift, & Leggio, 2011; Heilig & Egli, 2006). The Food and Drug Administration (FDA) has only approved disulfiram, naltrexone and acamprosate for AUD, and all these medications have limited efficacy (Edwards et al., 2011; Heilig & Egli, 2006).

Developing new drugs for AUD is therefore a high scientific and public health priority. There is a crucial need to identify novel drug targets that may lead to the discovery of new effective medications for AUD.

One source of new drug targets comes from research on the neurobiology of obesity, as alcohol- and food-seeking behaviors share some overlapping features and neural circuits (Tomasi & Volkow, 2013).

While alcoholism, obesity and binge eating are complex conditions with likely diverse genetic and environmental contributions to their etiologies (Tomasi & Volkow, 2013), it is notable that medications used to treat AUD often result in weight loss. For example, naltrexone, topiramate and ondansetron are used in the treatment of AUD and have also been utilized to treat obesity and/or eating disorders (Leggio et al., 2011). Therefore, research focused on identifying feeding-related pathways may be of utility in understanding the neurobiology of alcoholism, and may yield possible neuropharmacological targets for AUD. As outlined below, there is an increasing body of evidence supporting the notion that the ghrelin system may be a novel neuropharmacological target for AUD.

References:

Grant, B. F., Goldstein, R. B., Saha, T. D., Chou, S. P., Jung, J., Zhang, H., . . . Hasin, D. S. (2015).

Epidemiology of DSM-5 Alcohol Use Disorder: Results From the National Epidemiologic Survey on Alcohol and Related Conditions III. JAMA Psychiatry, 72(8), 757-766.

doi:10.1001/jamapsychiatry.2015.0584

Garbutt, J. C., West, S. L., Carey, T. S., Lohr, K. N., & Crews, F. T. (1999). Pharmacological treatment of alcohol dependence: a review of the evidence. JAMA, 281(14), 1318-1325. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/10208148

Edwards, S., Kenna, G. A., Swift, R. M., & Leggio, L. (2011). Current and promising pharmacotherapies, and novel research target areas in the treatment of alcohol dependence: a review. Curr Pharm Des, 17(14), 1323-1332. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/21524263

Heilig, M., & Egli, M. (2006). Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms. Pharmacol Ther, 111(3), 855-876. doi:10.1016/j.pharmthera.2006.02.001

Miller, E. K., & Cohen, J. D. (2001). An integrative theory of prefrontal cortex function. Annu Rev Neurosci, 24, 167-202. Retrieved from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_ uids=11283309

Tomasi, D., & Volkow, N. D. (2013). Striatocortical pathway dysfunction in addiction and obesity:

differences and similarities. Crit Rev Biochem Mol Biol, 48(1), 1-19.

doi:10.3109/10409238.2012.735642

Leggio, L., Addolorato, G., Cippitelli, A., Jerlhag, E., Kampov-Polevoy, A. B., & Swift, R. M. (2011). Role of feeding-related pathways in alcohol dependence: A focus on sweet preference, NPY, and ghrelin.

Alcohol Clin Exp Res, 35(2), 194-202. doi:10.1111/j.1530-0277.2010.01334.x https://www.ncbi.nlm.nih.gov/pubmed/10208148 https://www.ncbi.nlm.nih.gov/pubmed/21524263 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_

Period of Performance / Expected Delivery Date.

This is a two-year contract to maintain study drug GLWL-1 certification for clinical use.

• The first period noted in the quote as Phase 0 is the most critical and must be completed before August 26, 2022. A stability report must be received on or before August 26, 2022.

• The second period, Phase 6 months, A stability report must be received six months after contract award date. Specific deadlines will be discussed during contract award.

• The third period, Phase 12 months, A stability report must be received 12 months after contract award date. Specific deadlines will be discussed during contract award.

There will also be a second year, option period. In this final phase of the contract, A stability report must be received 24 months after the contract award date. Specific deadlines will be discussed during activation of the contract option.

4. Acquisition Authority. This acquisition is conducted under the authority of the Federal Acquisition Regulations (FAR) Subpart 13.106-1(b) Soliciting from a single source. (1) For purchases not exceeding the simplified acquisition threshold, contracting officers may solicit from one source if the contracting officer determines that the circumstances of the contract action deem only one source reasonably available (e.g., urgency, exclusive licensing agreements, or industrial mobilization).

5. Justification Rationale.

This study investigational drug, GLWL-1, is currently being used in an active clinical study with active research participants. GLWL-01 is set to expire on August 26, 2022. It is critical that stability testing is performed to recertify the drug and extend its expiration date so the clinical study may continue uninterrupted—maintaining participant safety and research integrity.

The purpose of stability testing is to provide evidence that the drug remains safe for human use.

Stability testing evaluates the drug and how it varies over time, testing a variety of environmental factors such as temperature and humidity levels. This helps establish storage conditions and shelf-life for the drug.

If GLWL-1 is not recertified and research stops, it would have a profound and costly impact on the clinical study. The investment of time, human capital (e.g., physicians, nurses, research technicians, counselors, etc..) and resources would be lost. Not only would there be a significant financial lost, but also a discontinuation of the study could jeopardize the relationship between physician and participant and compromise the data collected until this point. Because we work with a vulnerable population, active participants may refuse to continue participation in the study. This increases the need for Recruitment services to advertise, screen, and bring in new participants, thus increasing the financial impact on the clinical program further.

Only one source is available:

In addition to the justification above, we must use the source selected by the manufacturer of GLWL-1 (GLWL Research Inc). In fact, Alcami Corporation completed all previous stability testing for this drug.

Alcami Corporation has several years of propriety, confidential data related to GLWL-1’s safety and the CEO of the drug manufacturer has granted Alcami Corporation permission to share this data with NIDA to continue stability testing of the drug. No other source has this information.

Alcami Corporation must be used to confirm the continuity and consistency in the overall methodology and assay analyses, and ensure that all processes and procedures follow the original evaluation and clearance. It is also important to note that Alcami’s previous expertise led to generating the previous Stability Program work that was a critical component of the initial FDA IND filed by the manufacturer and of the other FDA IND filed by the NIH under which the NIDA clinical study is conducted.

Therefore, using the same exact methodologies/assays as those at Alcami will make sure that the future Stability Program conducted by Alcami as part of this study is consistent with the methodologies/assays already on filed in the FDA IND filed by the NIH. The mission of NIDA/NIH is to conduct the most rigorous, reproducible scientific work with the highest possible research integrity.

Using Alcami’s expertise and access to propriety data allows us to safely continue use of GLWL-1 in clinical research. Using a different company will jeopardize the research integrity and scientific rigor of this work and will not be feasible, given the very specific timeline, nature and scope of this requirement.

Project Officer Certification. The Project Officer, Technical or Requirements Personnel certifies that any data or information provided in support of this justification for the proposed acquisition has been reviewed and that to the best of our knowledge and belief is accurate and complete and the below signature recommends approval.

Project Officer Date

Contracting Officer Certification. The Contracting Officer certify that the justification for the proposed acquisition has been reviewed and that to the best of my knowledge and belief the information and/or data provided to support the rationale and recommendation for approval is accurate and complete and the below signature denotes approval.

Contracting Officer Date

a. Project Title. Manipulating Ghrelin signaling via GOAT inhibition in alcohol use disorder.