On January 18, 2022 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported an update on the on-going OPTIMIZE-1 clinical Phase Ib/II trial with the company’s lead asset, mitazalimab (Press release, Alligator Bioscience, JAN 18, 2022, View Source [SID1234605513]). All patients in the 450 µg/kg cohort have been dosed and there have been no adverse effects related to study medication has been reported. Dosing of the 900 µg/kg cohort has been initiated. The Phase 1b part of the study is expected to be completed during Q1 2022.

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OPTIMIZE-1, an open-label, multi-center phase Ib/II study is assessing the safety and efficacy of mitazalimab in combination with chemotherapy, mFOLFIRINOX, in patients with metastatic pancreatic ductal adenocarcinoma. First patient was dosed in Q3 2021 (press release). The study is designed to take full advantage of mitazalimab efficacy and tolerability profile administering higher and more frequent doses than competing molecules. This increases the likelihood of demonstrating clinical benefit to patients as a potential first-line treatment for metastatic pancreatic cancer in combination with mFOLFIRINOX. Patient recruitment is ongoing in sites France and Belgium. The study aims to enrol 67 patients with metastatic pancreatic cancer.

"I am happy to report that we continue to make great progress with our OPTIMIZE-1 trial," comments Søren Bregenholt, CEO of Alligator Bioscience. "We look forward to keeping the market regularly updated as the project advances."

The safety readout for OPTIMIZE-1 is expected to be announced in Q1 2022, with the interim readout in Q4 2022.

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.

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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 18, 2022 Sema4 (Nasdaq: SMFR), an AI-driven genomic and clinical data intelligence platform company, and OPKO Health, Inc. (Nasdaq: OPK) ("OPKO"), a multinational biopharmaceutical and diagnostics company, reported that they have signed a definitive agreement for Sema4 to acquire OPKO’s wholly owned subsidiary, GeneDx, Inc. ("GeneDx"), a leader in genomic testing and analysis, from OPKO (Press release, Opko Health, JAN 18, 2022, View Source [SID1234605547]). The acquisition strengthens Sema4’s leadership, growth, and scale for its market-leading health intelligence and genomic screening offerings. Together, Sema4 and GeneDx will be one of the largest and most advanced providers of genomic clinical testing in the U.S., with a projected $350 million in pro forma 2022 revenue.

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Following completion of the acquisition, Sema4 will be optimally positioned to partner with health systems and biopharma companies to further transform the standard of care throughout the patient health journey. GeneDx’s leadership in rare disease diagnostic and exome sequencing services brings more than 300,000 clinical exomes and over 2.1 million expertly annotated phenotypes to strengthen Sema4’s 12 million de-identified clinical records for Centrellis, its proprietary integrated health intelligence platform, and Traversa, its comprehensive genomic analysis platform for optimizing health screenings. Sema4 plans to leverage this combined health information database to transform patient care and therapeutic development and enable precision medicine for all.

"This acquisition gives us the opportunity to accelerate the use of genomics as standard of care by providing a deeper menu of precision medicine solutions to our health system partners to better meet their clinical needs," said Eric Schadt, PhD, Founder and CEO of Sema4. "Adding GeneDx’s comprehensive dataset and capabilities to our offerings enables us to inform on an even broader range of diseases, further closing the gap between the practice of medicine and the availability of more clinically actionable guidance. GeneDx’s operational prowess and market-leading cost structure in exome and genome sequencing will also help accelerate our path to improved gross margins and profitability. I am also delighted to welcome Katherine to our leadership team. She and her team’s world-class expertise will be critical to our continued growth and success."

Katherine Stueland, President and CEO of GeneDx and former CCO of Invitae, will be appointed as Sema4 co-CEO and is expected to join the Sema4 Board of Directors upon completion of the acquisition. She brings significant commercial and operational experience and will lead overall operational excellence and business planning, and will focus on the diagnostics business. Dr. Schadt will continue to serve Sema4 as co-CEO and as a member of the Board of Directors focusing on leading R&D and the IT platform components of Sema4, the strategic development of Sema4’s health intelligence capabilities, and partnerships with health systems and biopharma companies. Together as co-CEOs, Dr. Schadt and Ms. Stueland will drive overall strategy and direction of the company.

"We are excited to join forces with Sema4, a market leader in using genomic and clinical data to deliver precision medicine," said Ms. Stueland. "The complementary fit between our teams, missions, and capabilities is strong. We are eager to put those strengths to work and to make it easier to use data-driven insights to improve healthcare for all. I’m looking forward to partnering with Eric to create an unrivaled family health and health intelligence company, supporting patients making healthcare decisions throughout their lives, from pregnancy and newborn health to adult rare disease, risk assessment, and cancer care."

As part of the transaction, Sema4 has also announced that it has entered into definitive agreements for a $200 million private placement of Sema4 Class A shares from a syndicate of institutional investors, including Pfizer. The acquisition and the private placement (together, the "Transaction") are expected to close concurrently in the first half of 2022, subject to a Sema4 stockholder vote and other conditions to closing set forth in the definitive Transaction documents.

Dr. Schadt added: "We are excited to announce this investment with the support of several key institutions, including Pfizer. We believe that genomics and data, when harnessed in partnership with health systems, can be a powerful tool to enable precision medicine by bringing novel therapies to patients faster and more effectively. We hope that this investment may serve as a foundation for potential future collaborations."

Phillip Frost, MD, Chairman and CEO of OPKO, added: "We believe the sale of GeneDx to Sema4 will unlock untapped value and maximize the value of GeneDx for the benefit of OPKO shareholders. In addition to bolstering our cash position, we will have a significant equity stake in Sema4 at closing, ensuring OPKO and our shareholders continue to participate in the rapidly growing genomics market through a continued investment in GeneDx, which we believe is well positioned to deliver long-term success."

In conjunction with the Transaction, Jason Ryan, a member of Sema4’s Board of Directors, former CFO of Foundation Medicine and most recently Chief Operating and Financial Officer of Magenta Therapeutics (Nasdaq: MGTA), will assume the role of Executive Chair of Sema4’s Board of Directors. Mr. Ryan has outstanding leadership experience in the life sciences and biotechnology sectors, and an impressive background in finance and scaling businesses. Mr. Ryan succeeds Joshua Ruch, who will continue to serve on Sema4’s Board of Directors as the Chairperson of its Compensation Committee.

Based on Sema4’s closing stock price as of January 14, 2022, the purchase price is approximately $623 million, including in total upfront cash, stock consideration, and contingent consideration upon commercial milestones.

Sema4 Standalone Fiscal Year 2022 Guidance

Sema4 expects total revenue for fiscal year 2022 to be in the range of $215 million to $225 million, implying 23-29% growth excluding revenue associated with COVID-19, and Sema4 also expects to result over 350,000 tests in 2022 excluding COVID-19 tests. On December 15, 2021, Sema4 announced that it has decided to discontinue COVID-19 testing services by March 31, 2022 and therefore the company expects an immaterial amount of revenue from COVID-19 in 2022.

Acquisition Terms

Under the terms of the agreement, Sema4 will acquire GeneDx for an upfront payment of $150 million in cash plus 80.0 million shares in Sema4, with up to an additional $150 million revenue-based milestones over the next two years (which will be payable in cash or Sema4 shares at Sema4’s discretion). Based on the closing stock price of Sema4 as of January 14, 2022, the total upfront consideration represents approximately $473 million, and the total aggregate consideration including potential milestones is approximately $623 million. The acquisition, which has been unanimously approved by the Boards of Directors of both Sema4 and OPKO, is expected to close in the second quarter of 2022, subject to customary closing conditions including approval by the stockholders of Sema4.

Private Placement

In connection with the acquisition, Sema4 has also entered into definitive agreements for a private placement financing to sell $200 million in Class A common stock at a price of $4.00 per share from a syndicate of institutional investors, including Pfizer.

The private placement is expected to substantially close concurrently with close of the acquisition, subject to the satisfaction of customary closing conditions.

Advisors

Goldman Sachs & Co. LLC. acted as financial advisor and Fenwick & West LLP served as legal counsel to Sema4 on the Transaction. J.P. Morgan acted as lead financial advisor and Cowen acted as financial advisor to OPKO on the Transaction. Greenberg Traurig, P.A. served as OPKO’s legal counsel. Goldman Sachs & Co. LLC. served as lead placement agent on the private placement. Jefferies LLC, Cowen, and BTIG, LLC also served as placement agents.

Conference Call and Webcast Details

Management will host a conference call and webcast today at 8:00 a.m. ET to discuss the transaction. Following prepared remarks, management will respond to questions from analysts, subject to time limitations.

The live webcast of the call and slide deck may be accessed by visiting the investors section of Sema4’s website at ir.sema4.com. A replay of the webcast and conference call will be available shortly after the conclusion of the call and will be archived on Sema4’s website.

On January 18, 2022 Akeso reported that Ligufalimab combined with Ivonescimab has obtained approval from the Center for Drug Evaluation (CDE) of the National Medical Products Administration of the People’s Republic of China (”China”) to initiate a Phase Ib/II clinical trial with or without chemotherapy for the treatment of advanced malignant tumors, with an aim to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and anti-tumor activity of Ligufalimab combined with Ivonescimab combined with or without chemotherapy for the treatment of advanced malignant tumors (Press release, Akeso Biopharma, JAN 18, 2022, View Source [SID1234605606]).

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The main target subjects of the phase II clinical trial were patients with gastrointestinal tumors. Previously, a phase Ib/II clinical trial of Ligufalimab combined with Ivonescimab has been initiated with main target subjects of patients with head and neck malignant tumors.

Related statistics have shown that malignant tumors have become the major cause of death in the population of China, where deaths from malignant tumors account for approximatelyn23.91% of deaths from all causes of the population. The five-year relative survival rate of malignant tumors in China is approximately 40.5%, which is still far from developed countries. In addition, gastrointestinal tumors account for six out of the top ten death rate of advanced malignant tumors. Among which, treatments for advanced gastric cancer, biliary malignant tumors, pancreatic cancer and other common gastrointestinal tumors are limited and the efficacy is not high, resulting in a huge gap of clinical demand.

Related studies have shown that Ivonescimab can simultaneously stimulate anti-tumor immune response and inhibit tumor angiogenesis through activation of T cells. Since the over-expression of VEGF in the tumor microenvironment has immunosuppressive effects, the use of a bi-specific antibody that blocks both PD-1 and VEGF can achieve synergistic anti-tumor effects of PD-1/PD-L1 antibodies and anti-VEGF antibodies. It is expected to achieve good clinical efficacy and safety. Currently, anti-PD-1/PD-L1 antibody drugs on the market or under research combined with chemotherapy has shown certain clinical benefits for gastrointestinal tumors. For non-small cell lung cancer and hepatocellular carcinoma, the combination of anti-PD-1/PD-L1 antibodies with anti-VEGF antibodies has shown notable synergistic effects.

Related studies have also shown that combination therapy with anti-PD-1 drugs and targeted CD47 drugs yields synergistic antitumor effect through activation of both innate and adaptive immune response, and has demonstrated satisfactory anti-tumor effect in some of the patients with solid tumors with no additional safety risk. CD47 up-regulation can inhibit the phagocytosis of macrophages and the anti-tumor effect of VEGF/VEGFR inhibitors. At the same time, anti-VEGF/VEGFR treatment can also induce CD47 up-regulation, thereby inhibiting the anti-tumor function of macrophages. Therefore, blocking both VEGF and CD47 can effectively inhibit the immunosuppressive pathway induced by anti-angiogenesis therapy (CD47 up-regulation) while enhancing the phagocytosis of macrophages to improve the anti-tumor efficacy.

Therefore, the combination therapy of Ligufalimab and Ivonescimab is expected to activate both innate and adaptive immune pathways, so to achieve the synergistic effect of inhibiting the three tumor immune targets of PD-1, VEGF and CD47 through the combination of the two drugs, thus achieving better anti-tumor effects as compared with existing therapies. Furthermore, based on the statistics of the in vitro and in vivo pharmacodynamics and toxicology studies of Ligufalimab and Ivonescimab, the anti-tumor activity and the controlled safety profile in several clinical trials of different types of tumors, it is expected that the combination of Ivonescimab and Ligufalimab and/or chemotherapy will have a positive effect for the treatment of gastrointestinal tumors.

Currently, Ivonescimab has taken the lead in entering the phase III clinical trial globally, and Ligufalimab is also one of the world’s leading CD47 monoclonal antibodies in clinical research and development progress. The clinical trial of Ligufalimab combined with Ivonescimab in the treatment of head and neck malignant tumors and gastrointestinal tumors is another embodiment of the Company’s continuous exploration of the clinical and commercial value of its rich drug pipeline.

On January 18, 2022 Evaxion Biotech A/S (NASDAQ: EVAX), a clinical-stage biotechnology company specializing in the development of AI-driven immunotherapies to improve the lives of patients with cancer and infectious diseases, reported that it has received clearance from the Australia Therapeutic Goods Administration to initiate a Phase 2b trial of its patient specific cancer immunotherapy EVX-01 in combination with Merck & Co., Inc.’s (known as MSD outside the United States and Canada) anti-PD-1 therapy KEYTRUDA (pembrolizumab) (Press release, Evaxion Biotech, JAN 18, 2022, View Source [SID1234605531]).

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The open label, single arm trial will evaluate the efficacy and safety of EVX-01 in combination with KEYTRUDA in approximately 100 checkpoint inhibitor treatment naïve adults with unresectable or metastatic melanoma, with overall response as the primary endpoint. The study is expected to be initiated in Q2. Evaxion will be responsible for the conduct of the study and Merck & Co., Inc. will supply all of the necessary KEYTRUDA and will continue to collaborate as the data mature.

Lars Wegner, CEO of Evaxion, said: "Australian clearance for our Phase 2b trial of our lead product EVX-01 is a significant step forward for Evaxion and our exciting pipeline of immunotherapies. Data from the Phase 1/2a trial have shown that EVX-01 may be able to dramatically improve the treatment landscape in melanoma and possibly other cancers and we are excited to continue the clinical progress of our lead drug candidate EVX-01 in collaboration with Merck. This new Phase 2b trial, combining EVX-01 and KEYTRUDA, addresses a significant medical need and a potential multibillion dollar market. There could be potential further benefits from combining EVX-01 with checkpoints inhibitors such as KEYTRUDA, and so this study may enable expansion into many other types of cancers, addressing a market of well over $100 billion."

An ongoing Phase 1/2a trial is investigating EVX-01, a novel patient specific cancer neoepitope immunotherapy based on Evaxion’s proprietary PIONEER AI technology, for the treatment of patients with melanoma. Data from this trial has shown that 67% of the nine patients benefited from EVX-01 in combination with anti-PD-1 for the treatment of metastatic melanoma, compared to the historical data of only 40% benefiting from the checkpoint inhibitor alone. 22% of the patients in the trial achieved a complete response with EVX-01 in combination with anti-PD-1.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Kenilworth, NJ, USA.