On September 24, 2021, Ensysce Biosciences, Inc. ("Ensysce" or the "Company") entered into a Securities Purchase Agreement (the "SPA") for an aggregate financing of $15 million with institutional investors. A first closing under the SPA occurred on September 24, 2021 and was reported in a Current Report filed on September 27, 2021 and a second closing under the SPA occurred on November 5, 2021 and was reported in a Current Report filed on November 10, 2021. At the first closing, the Company issued to the investors (i) senior secured convertible promissory notes in the aggregate principal amount of $5.3 million for an aggregate purchase price of $5 million (collectively, the "Notes") and (ii) warrants (collectively, the "Warrants") to purchase 361,158 shares of the Company’s common stock, par value $0.0001 per share (the "Common Stock") in the aggregate. At the second closing, the Company issued to the institutional investors referenced above, (i) Notes in the aggregate principal amount of $10.6 million for an aggregate purchase price of $10 million and (i) Warrants to purchase 722,317 shares of the Common Stock in the aggregate. Under the SPA, the conversion price for converting Notes into the Company’s common stock is $5.87 per share, subject to adjustment under certain events.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On December 27, 2021, the parties to the SPA agreed to a Letter Agreement amending the SPA ("Letter Agreement"). Under the terms of the Letter Agreement, holders of the Notes were entitled to convert notes at an exercise price of $4.50 per share of Company Common Stock for fourteen trading days, commencing December 28, 2021 and ending January 14, 2022. Under the terms of the Letter Agreement, following this period, the initial conversion price of $5.87 will apply. There was no change to the exercise price of the Warrants. The Letter Agreement also included certain conditions that the Company must satisfy in connection with the transaction. The Letter Agreement expired on January 14, 2022.

On January 16, 2022, the parties to the SPA agreed to a Second Letter Agreement amending the SPA ("Second Letter Agreement"). Under the terms of the Second Letter Agreement, holders of the Notes may convert notes at an exercise price of $3.80 per share of Company Common Stock commencing January 18, 2022 and ending February 11, 2022. Following this period, the initial conversion price of $5.87 will apply. There is no change to the exercise price of the Warrants. The Second Letter Agreement also includes certain conditions that the Company must satisfy in connection with the transaction.

The Company has registered with the Securities and Exchange Commission (the "SEC") the resale of the shares of Common Stock issuable upon conversion of the Notes as well as the shares of Common Stock issuable upon the exercise of the Warrants pursuant to the Registration Rights Agreement, dated September 24, 2021, by and among the Company and the purchasers signatory to the SPA.

On January 19, 2022 CureLab Oncology,a clinical-stage biotech company, and the American Eurasian Cancer Alliance (AECA), reported to have partnered to expand research and to fast-track next-generation therapies for ovarian cancer in Eurasia (Press release, CureLab Oncology, JAN 18, 2022, View Source [SID1234605529]). The alliance aims to accelerate the clinical trials of CureLab Oncology’s Elenagen, an experimental DNA therapy, by leveraging the broad reach and influence of the AECA in the region.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Since its inception in 2001, the AECA has implemented its vision of decreasing the burden of cancer in U.S. and Eurasian populations through strategic partnerships and programs that promote cancer research and enhance cancer control in the region. AECA’s reach extends across the Russian Federation, Central Asia (Kazakhstan, Uzbekistan, Kyrgyzstan, Tajikistan), Central Europe (Ukraine, Moldova, Belarus), the Baltics (Lithuania, Latvia, Estonia), and Caucasia (Armenia, Georgia, Azerbaijan).

In Belarus, for example, the AECA and CureLab Oncology have already teamed to help launch the International Gynecologic Cancer Society (IGCS) program within the country. CureLab’s ongoing clinical research studies of Elenagen therapy at the N.N. Alexandrov National Cancer Centre of Belarus have demonstrated encouraging preliminary results in triple-negative breast cancer and platinum-resistant ovarian cancer patients.

"We want to build on our program in Belarus and bring the fight against ovarian cancer to more countries in the region," said Alexander Shneider, Ph.D., CEO of CureLab Oncology. "The AECA’s commitment to strengthening global cancer research, promoting research training and education, and translating research into policy and programs will enable us to achieve that goal. Importantly, this is a two-way highway—if not a Möbius strip. An invention made by a team of American, Israeli, and Italian scientists came to Russia and Belarus for pre-clinical and early-stage clinical development, and now we are bringing it back to the United State for phase II clinical trials."

"For decades, AECA has been on the cutting edge of scientific and technological oncology advancements, and we’re thrilled to continue this important endeavor with CureLab Oncology," said Dr. Sophia Michaelson, executive director of the American Eurasian Cancer Alliance.

"Leveraging AECA’s strong partnerships throughout the Eurasian region has already helped to advance this experimental treatment agenda, and we are hopeful continued research will yield results that could be beneficial for the global cancer control community.

On January 18, 2022 Abbisko Therapeutics of Shanghai reported a global collaboration worth up to $258 million with Lilly to continue discovery and development of novel molecules for cardiometabolic diseases (Press release, ChinaBio, JAN 18, 2022, View Source [SID1234605528]). Abbisko will be responsible for further discovery/development of molecules that modulate a novel target using its proprietary R&D platform. If Abbisko successfully advances the compounds to their endpoints, Lilly will have the right to take over commercialization. If Lilly elects not to advance the compounds, Abbisko will have global rights to the candidate and pay milestones and royalties to Lilly.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On January 18, 2022 Celularity Inc. (Nasdaq: CELU) ("Celularity"), a clinical-stage biotechnology company developing placental-derived off-the-shelf allogeneic cell therapies, reported the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for its genetically modified cryopreserved human placental hematopoietic stem cell-derived natural killer (NK) cell therapy, CYNK-101, which is being developed in combination with standard chemotherapy, trastuzumab and pembrolizumab in patients in first-line locally advanced unresectable or metastatic HER2/neu positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (Press release, Celularity, JAN 18, 2022, View Source [SID1234605527]). CYNK-101 is an investigational genetically modified NK cell therapy designed to synergize with approved antibody therapeutics through enhanced antibody-dependent cellular cytotoxicity (ADCC).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Robert Hariri, M.D., Ph.D., Founder, Chairperson and Chief Executive Officer of Celularity, said, "We are extremely excited to receive this fast track designation and the support from the FDA for our investigational genetically modified NK cell therapy in the first-line setting of G/GEJ cancers. CYNK-101 is built on the foundation of our unique placental-derived source material, which as compared to other cell sources, has naturally enhanced proliferative potential (or "stemness"), that has been shown to be a determinant of persistence and efficacy potential. Using novel genetic engineering, we have enhanced the ability of CYNK-101 cells to synergize with approved antibodies and provide a novel and potentially non-cross resistant therapy to improve the lives of patients with G/GEJ cancers as well as a broad range of other indications."

"The addition of immune-based therapy of blocking PD-1 with a checkpoint inhibitor (pembrolizumab) to the prior standard of care (chemotherapy and traztuzumab) has recently been shown to be of benefit in patients with first-line HER2/neu positive unresectable G/GEJ cancer," added Andrew Pecora, M.D., President of Celularity. While overall response rates in first-line G/GEJ treated with the triple combination of chemotherapy, traztuzumab and pembrolizumab were significantly greater with the addition of pembrolizumab (74.4% vs 51.9%; p=0.000006; Keynote-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer; Janjigian Y et al., Nature 600, 727-730 (2021), complete response rates remained modest, however (11.3%). "Our recently accepted IND enables the assessment to possibly further improve outcomes in G/GEJ treated with triple combination therapy by adding CYNK-101 cells, a potentially non-cross resistant therapy (enhanced ADCC, direct NK cell tumor killing and help of T cell function and memory) after initially cytoreducing the tumor mass and potentially diminishing resistance in the tumor microenvironment with combined chemotherapy, traztuzumab and pembrolizumab "induction" followed by reinduction and maintenance with CYNK-101 cells in combination with traztuzumab and pembrolizumab."

About Fast Track Designation

Fast Track Designation is an FDA process designed to facilitate the development and expedite the review of new drugs that are intended to treat a serious condition and have the potential to address unmet medical needs. The purpose of Fast Track designation is to expedite the process of getting important new drugs to patients. The designation may offer frequent interactions with the FDA review team on the product’s development and the product may be eligible for rolling review and priority review if certain criteria are met.

About Gastric Cancer

Gastric cancer is the fifth most common cancer worldwide(1). Despite recent improvements in treatment quality and options, advanced gastric cancer remains one of the hardest to cure cancers, with a median overall survival (OS) of 10–12 months and a five-year OS of approximately 5–20%. In May 2021, the U.S. FDA granted accelerated approval to pembrolizumab in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2+ G/GEJ cancers (2)

REFERENCES

Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68 (6):394–424. doi:10.3322/caac.21492.
FDA grants accelerated approval to pembrolizumab for HER2-positive gastric cancer. Access here: View Source Accessed January 17, 2022.
About CYNK-001

Celularity’s lead therapeutic program based on its placental-derived unmodified NK cell type is CYNK-001, an allogeneic unmodified NK cell being developed as a treatment for hematologic malignancies, solid tumors, and infectious diseases. CYNK-001 is a cryopreserved allogeneic off-the-shelf cell therapy enriched for CD56+/CD3- NK cells expanded from human placental CD34+ cells. The safety and efficacy of CYNK-001 have not been established, and CYNK-001 has not been approved for any use by the U.S. Food and Drug Administration or any other analogous regulatory authority.

On January 18, 2022 Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported the appointment of Syed Rizvi, M.D., to the newly created position of chief medical officer (Press release, Caribou Biosciences, JAN 18, 2022, View Source [SID1234605526]). Dr. Rizvi has more than two decades of experience in all stages of drug development, from clinical strategy and execution through regulatory submissions to support approval and commercialization of several cancer treatments, including two autologous CAR-T cell therapies ABECMA and BREYANZI.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Syed’s extensive industry knowledge, strategic insight, and significant leadership experience in the development of oncology cell therapies will be valuable to Caribou as we advance our pipeline of sophisticated genome-edited allogeneic therapeutics," said Rachel Haurwitz, Ph.D., Caribou’s president and chief executive officer. "In 2022, we plan to disclose initial data from our ANTLER Phase 1 clinical trial evaluating CB-010, file an IND application for our second CAR-T cell product candidate, CB-011, and announce target selection for our first CAR-NK cell therapy, CB-020. We have a transformative year ahead of us and I am delighted to welcome Syed to the Caribou team."

"I am thrilled to join Caribou, a pioneering company at the cutting edge of CRISPR genome editing and allogeneic cell therapy discovery and development," said Dr. Rizvi. "Caribou’s promising pipeline and highly specific Cas12a chRDNA technology have the potential to revolutionize the treatment of patients with cancer and may have broader applications. I am excited to lead Caribou’s clinical development initiatives and look forward to working with our experienced leadership team, dedicated colleagues, investigators, and regulatory authorities to achieve Caribou’s mission to provide innovative, transformative therapies for patients with devastating diseases."

Dr. Rizvi most recently served as chief medical officer of Chimeric Therapeutics, where he led the strategy and execution of clinical development programs for the company’s T cell and NK cell therapy platforms and helped build the pipeline. Previously, he worked for Legend Biotech, a cell therapy company, serving as head and vice president of clinical development, clinical operations, safety, data sciences, project management, and medical affairs, and he served as co-chair of the joint development committee for the Legend-Janssen collaboration. At Legend, he led the development of Cilta-cel, an autologous BCMA CAR-T cell therapy, as well as other cell therapies. Earlier, he worked for Celgene Corporation (now a Bristol Myers Squibb Company), serving as the head of global medical affairs for CAR-T cell programs and head of hematology and immuno-oncology for U.S. medical affairs. At Celgene, he was responsible for the strategic direction and management of Celgene’s CAR-T cell and immuno-oncology therapy portfolios. He built a comprehensive clinical research alliance and developed an immuno-oncology network with researchers to harness scientific learnings and advance clinical development for targeted patient outcomes. At Celgene, he was responsible for the global medical strategy supporting the clinical development of ABECMA in multiple myeloma and BREYANZI in lymphoma, both autologous CAR-T cell therapies. He previously held global clinical leadership positions of increasing responsibility for oncology programs at Novartis, Merck, and Genta, Inc.

Dr. Rizvi received his medical degree from Dow Medical College and spent several years in direct patient care before joining Saint Vincent’s Comprehensive Cancer Center in New York. Dr. Rizvi has authored numerous peer-reviewed publications and is a member of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), the American Society of Hematology (ASH) (Free ASH Whitepaper), the American Society for Transplantation and Cellular Therapy, and other professional organizations.

About Caribou’s Novel Next-Generation CRISPR Platform

CRISPR genome editing uses easily designed, modular biological tools to make DNA changes in living cells. There are two basic components of Type II CRISPR systems: the nuclease protein that cuts DNA and the RNA molecule(s) that guide the nuclease to generate a site-specific, double-stranded break, leading to an edit at the targeted genomic site. CRISPR systems occasionally edit unintended genomic sites, known as off-target editing, which may lead to harmful effects on cellular function and phenotype. In response to this challenge, Caribou has developed chRDNAs (pronounced "chardonnays"), RNA-DNA hybrid guides that direct substantially more precise genome editing compared to all-RNA guides. Caribou is deploying the power of its Cas12a chRDNA technology to carry out high efficiency multiple edits, including multiplex gene insertions, to develop CRISPR-edited therapies.