On May 9, 2022 Sesen Bio (Nasdaq: SESN), a late-stage clinical company developing targeted fusion protein therapeutics for the treatment of patients with cancer, reported operating results for the first quarter ended March 31, 2022 (Press release, Seagen, MAY 9, 2022, View Source [SID1234613908]). During the quarter, the Company continued to engage with the US Food and Drug Administration (FDA) to identify an anticipated regulatory path toward potential resubmission of a Biologics License Application (BLA) for Vicineum for the treatment of non-muscle invasive bladder cancer (NMIBC). The Company has also initiated a process to review strategic alternatives with the goal of maximizing shareholder value.

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US Regulatory Update

On March 28, 2022, Sesen Bio participated in a Type C Meeting with the FDA. During the meeting, the FDA agreed to a majority of the Company’s proposed protocol and statistical analysis plan design elements for an additional Phase 3 clinical trial that it plans to conduct for potential resubmission of a BLA for Vicineum for the treatment of NMIBC. The Company plans to meet with the FDA in mid-2022 to align on the remaining outstanding items related to the additional Phase 3 clinical trial, and intends to request that meeting in the coming weeks.
In addition to working with the FDA to align on a study design, the Company has been addressing comments related to Chemistry, Manufacturing and Controls (CMC) that were included in the Complete Response Letter (CRL) for the BLA for Vicineum for the treatment of bacillus Calmette-Guérin (BCG)-unresponsive NMIBC. The Company has completed technical work on several of the key CMC comments and is continuing to make progress on the remaining items. The Company’s responses to the CMC comments will ultimately be reviewed by the FDA upon a potential BLA resubmission.

Other Business Updates

On January 6, 2022, Sesen Bio disclosed that it achieved a $20 million milestone payment pursuant to the Company’s exclusive license agreement (Roche License Agreement) with Roche for legacy Interleukin-6 (IL-6) antagonist antibody technology owned by Sesen Bio. Following this milestone payment, Sesen Bio has cumulatively received $50 million in upfront and milestone payments, with an additional $220 million in potential future milestone payments, as well as royalty payment obligations on future sales, remaining under the Roche License Agreement. As part of the Roche License Agreement, Roche also maintains the right to fully acquire the IL-6 technology.
On May 3, 2022, Sesen Bio announced that it had initiated a process to review strategic alternatives with the goal of maximizing shareholder value. Potential strategic alternatives to be explored and evaluated during the review process may include the sale of the Company, a merger, acquisition or other business combination, a strategic partnership with one or more parties, or the licensing, sale or divestiture of some of the Company’s proprietary technologies. The Company is actively working with an investment bank in this process. Pending any decision to undertake any strategic alternative, the Company is continuing its development activities in accordance with its existing business strategy.
On June 22, 2022, Sesen Bio will hold its Annual Meeting of Stockholders, one of the primary purposes of which will be to approve a proposal for a reverse stock split, which includes a proportionate reduction in authorized shares of common stock. The proposed reverse stock split, if approved, should allow the Company to remain listed on the Nasdaq Global Market, which should increase the range and attractiveness of strategic alternatives that the Company is able to consider to maximize shareholder value.
First Quarter 2022 Financial Results

Cash Position: Cash, cash equivalents and restricted cash were $169.8 million as of March 31, 2022, compared to $110.0 million as of March 31, 2021.
R&D Expenses: Research and development expenses for the first quarter of 2022 were $4.8 million compared to $6.1 million for the same period in 2021. The decrease of $1.3 million was primarily due to lower costs associated with technology transfer and manufacturing ($1.4 million), regulatory and clinical consulting fees ($0.6 million) and license milestone fees ($0.6 million), which were partially offset by increases in employee-related compensation, primarily driven by increased headcount and the retention program implemented in the fourth quarter of 2021 ($1.2 million), and other R&D expenses ($0.1 million).
G&A Expenses: General and administrative expenses for the first quarter of 2022 were $9.0 million compared to $5.3 million for the same period in 2021. The increase of $3.7 million was due primarily to increases in legal expenses related, in part, to the independent internal review completed in February 2022 ($3.0 million), employee-related compensation, primarily driven by increased headcount and the retention program implemented in the fourth quarter of 2021 ($1.1 million), insurance expense ($0.1 million) and other general expenses ($0.2 million). This was partially offset by a decrease in consultant fees incurred in preparation for commercial launch as a result of the subsequent CRL received in August 2021 ($0.7 million).
Net Loss: Net loss was $0.8 million, or $0.00 per basic and per diluted share, for the first quarter of 2022, compared to net loss of $55.5 million, or $0.35 per basic and diluted share, for the same period in 2021. The decrease of $54.7 million in net loss was primarily attributable to the non-cash decrease in fair value of contingent consideration ($61.1 million), partially offset by decreased license and related revenue recognized ($4.3 million).
About Vicineum
Vicineum, a locally administered fusion protein, is Sesen Bio’s lead product candidate being developed for the treatment of non-muscle invasive bladder cancer (NMIBC). Vicineum is comprised of a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas Exotoxin A. Vicineum is constructed with a stable, genetically engineered peptide tether to ensure the payload remains attached to the antibody binding fragment until it is internalized by the cancer cell. This fusion protein design is believed to decrease the risk of toxicity to healthy tissues, thereby improving its safety. In prior clinical trials conducted by Sesen Bio, EpCAM has been shown to be overexpressed in NMIBC cells with minimal to no EpCAM expression observed on normal bladder cells. Sesen Bio is currently in the follow-up stage of a Phase 3 clinical trial in the US for the treatment of BCG-unresponsive NMIBC. In February 2021, the FDA accepted the Company’s Biologics License Application (BLA) file for Vicineum for the treatment of BCG-unresponsive NMIBC, granted Priority Review for the BLA and set a Prescription Drug User Fee Act (PDUFA) date of August 18, 2021. On August 13, 2021, the Company received a Complete Response Letter (CRL) from the FDA regarding its BLA for Vicineum. After meeting with the FDA, the Company plans to conduct an additional Phase 3 clinical trial for Vicineum for the treatment of NMIBC in connection with the potential resubmission of a BLA. The Company plans to request a meeting with the FDA in the coming weeks to align on the remaining outstanding items related to the additional Phase 3 clinical trial. Additionally, Sesen Bio believes that cancer cell-killing properties of Vicineum promote an anti-tumor immune response that may potentially combine well with immuno-oncology drugs, such as checkpoint inhibitors. For this reason, the activity of Vicineum in BCG-unresponsive NMIBC is also being explored at the US National Cancer Institute in combination with AstraZeneca’s immune checkpoint inhibitor durvalumab.

On May 9, 2022 OPKO Health, Inc. (NASDAQ: OPK), a multinational biopharmaceutical and diagnostics company, reported the acquisition of ModeX Therapeutics, Inc. a privately held biotechnology company focused on developing innovative multi-specific immune therapies for cancer and infectious diseases (Press release, Opko Health, MAY 9, 2022, View Source [SID1234613907]). OPKO acquired ModeX for $300 million in OPKO common stock .

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Founded in October 2020 with headquarters in Natick, Mass., ModeX Therapeutics has developed highly flexible multi-specific antibody technology platforms with broad targeting and functional capabilities, simpler manufacturing and potentially better specificity and safety, providing significant differentiation from competing platforms. The design of these multi-specifics is amenable to gene-based delivery by mRNA or DNA vectors. The ModeX product portfolio includes cancer immunotherapies that combine four specificities into one protein to improve targeting and immune killing, as well as masking or "stealth" technology to improve tumor-specific killing and reduce side effects. For viral diseases, the lead targets of a broad and potent multi-specific antibody portfolio include HIV and SARS-CoV-2. A vaccine for Epstein-Barr virus is also in development.

"The acquisition of ModeX Therapeutics significantly broadens our technology foundation and expands our product pipeline to include multi-specific multi-functional antibodies focused on a range of cancers and infectious diseases, with applicability to other therapeutic areas. We believe the promise of better outcomes for patients treated with these multi-specific antibodies represents a next generation of large molecule therapeutics and the next chapter of OPKO," said Phillip Frost, M.D., Chairman and Chief Executive Officer of OPKO. "We welcome ModeX’s co-founders Dr. Zerhouni and Dr. Nabel, as well as Alexis Borisy to our Board of Directors, and Dr. Zerhouni and Dr. Nabel to OPKO’s executive management team. The ModeX executive team brings to OPKO a wealth of experience, knowledge and industry contacts, which we expect will have a tremendous long-term positive impact on OPKO as we advance their technology and product pipeline and leverage potential synergies with our current portfolio in diagnostics and therapeutics."

Elias Zerhouni, M.D., Co-Founder and Chairman of the Board of ModeX, has been appointed President and Vice Chairman of the Board of Directors of OPKO. Dr. Zerhouni brings extensive experience in academia, government and industry as a leading authority on emerging trends and issues in medical care and biomedical research and development. A physician scientist with an academic background in imaging and biomedical engineering, Dr. Zerhouni most recently served as President of Global Research & Development and Executive Vice President of Sanofi. Dr. Zerhouni also served as Director of the National Institutes of Health (NIH), Senior Fellow for Global Health Research at the Bill and Melinda Gates Foundation, Presidential U.S. Envoy for Science and Technology, and Professor and Chair of the Russell H. Morgan Department of Radiology and Biomedical Engineering, Executive Vice Dean and Dean for Research at the Johns Hopkins School of Medicine. Dr. Zerhouni was elected to the National Academy of Medicine and to the National Academy of Engineering. He serves on the Board of the Lasker Foundation, the Foundation for NIH, the Davos Alzheimer’s Collaborative and Research!America. He received the 2017 Scripps Executive of the Year Award for the pharmaceutical industry and the French Legion of Honor in 2008. He has been a director of Danaher Corporation since 2009.

"Being part of OPKO represents a transformative opportunity for both companies. We anticipate it will accelerate ModeX’s product pipeline focused on unmet needs in oncology and infectious diseases and the development of our innovative technologies, and also will take advantage of synergies with OPKO’s programs," said Dr. Zerhouni. "ModeX has operated quietly since we were founded 18 months ago on the basis of over 10 years of prior foundational work. We have assembled a world-class executive team with outstanding public and private sector leadership experience to advance our programs. Our lead drug candidate is already in the clinic while several others in late preclinical stages are expected to enter clinical development in 2023. We were enticed to join OPKO by its leadership’s vision and enthusiasm for strengthening our mutual potential for breakthrough innovation."

Gary Nabel, M.D., Ph.D., Co-Founder, President and Chief Executive Officer of ModeX, has been appointed Chief Innovation Officer of OPKO and joins OPKO’s Board of Directors. Dr. Nabel, a renowned virologist and immunologist, served as Chief Scientific Officer and Senior Vice President of Sanofi where he directed the breakthrough laboratory that developed tri-specific products now in early clinical development. He is the founding director of the NIH’s Vaccine Research Center, working on vaccines and broadly neutralizing antibodies against HIV, influenza, SARS, Ebola, Chikungunya and Epstein-Barr virus. He was previously an investigator at the Howard Hughes Medical Institute at the University of Michigan. In recognition of his expertise at the forefront of virology, immunology, gene therapy and molecular biology, Dr. Nabel was elected to the National Academy of Medicine, is a fellow of the American Association of Physicians and the American Academy of Arts Sciences, and was awarded the Geoffrey Beene Builders of Science Award from Research!America.

Alexis Borisy, the Lead Independent Director of ModeX, also joins OPKO’s Board of Directors. Mr. Borisy is a leading biotechnology entrepreneur and investor with more than 25 years of experience, including founding, serving as Chief Executive Officer and/or Chairman of nine NASDAQ-listed companies. He co-founded and served as either the Chief Executive Officer or Chairman of Blueprint Medicines, Foundation Medicine, Relay Therapeutics, Tango Therapeutics, Celsius Therapeutics and CombinatoRx.

With the additions of Dr. Zerhouni, Dr. Nabel and Mr. Borisy to OPKO’s Board, the number of Directors expands to 13.

Conference Call & Webcast Information

Management will discuss this transaction and answer questions during the company’s previously scheduled first quarter 2022 conference call, to be held today at 4:30 p.m. Eastern time. Participants can pre-register for the conference call using this link. Callers who pre-register will be given a unique PIN to gain immediate access to the call and bypass the live operator. Participants may register at any time, including up to and after the call start time. Those unable to pre-register may participate by dialing (866) 777-2509 (U.S.) or (412) 317-5413 (International). A webcast of the call may also be accessed at OPKO’s Investor Relations page and here.

A telephone replay will be available until May 16, 2022 by dialing (877) 344-7529 (U.S.) or (412) 317-0088 (International) and providing the passcode 6587528. A webcast replay will be available beginning approximately one hour after the completion of the live conference call here.

On May 9, 2022 MobileODT, a leading Israeli FemTech company, reported that it has been selected as the winner of the "Best New Imaging Technology Solution" award in the sixth annual MedTech Breakthrough Awards program conducted by MedTech Breakthrough, an independent market intelligence organization that recognizes the top companies, technologies and products in the global health and medical technology market (Press release, MobileODT, MAY 9, 2022, https://www.mobileodt.com/press-releases/mobileodt-recognized-for-imaging-technology-innovation-in-2022-medtech-breakthrough-awards-program/ [SID1234613906]).

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MobileODT is creating a new paradigm in cervical cancer screening and diagnostics at the point of care. MobileODT’s EVA System combines advanced imaging, data, and software applications. EVA is a digital mobile colposcope powered by Artificial Intelligence and telehealth components.

The company’s EVA VisualCheck AI technology is a clinical decision support tool that harnesses the power of artificial intelligence (AI) and Machine Learning (ML) to perform cervical cancer screening at scale. It offers an alternative screening modality to the current standard of care, with significantly improved accuracy and speed – returning results in under 60 seconds.

"It is a great honor to be recognized with this award from MedTech Breakthrough. We are the only company in the world with an AI capability in cervical cancer screening and the only company that can perform screening at scale – and this 2022 MedTech Breakthrough Award is a strong validation of our momentum," said Leon Boston, CEO of MobileODT. "With such unprecedented screening at scale, this can be life-saving for many women around the world. We stand ready to support the World Health Organization’s strategic mission to eliminate cervical cancer by 2030."

The mission of the MedTech Breakthrough Awards is to honor excellence and recognize the innovation, hard work, and success in a range of health and medical technology categories, including Telehealth, Clinical Administration, Patient Engagement, Electronic Health Records (EHR), Virtual Care, Medical Devices, Medical Data and many more. This year’s program attracted more than 3,900 nominations from over 15 different countries throughout the world.

"The unfortunate reality is that many cervical cancer cases occur because of a lack of timely screening. With over 300,000 women dying from cervical cancer each year, timely follow-up and the ability to receive the results immediately at the point of care, represents a complete game-changer," said James Johnson, managing director, MedTech Breakthrough. "The EVA VisualCheck system serves as a "breakthrough" solution that is quick and easy to use, allowing for the ability to screen more patients and predict results with high accuracy. Congratulations to MobileODT on this extremely important win – you’re our choice for ‘Best New Imaging Technology Solution.’"

On May 9, 2022 Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the "Company"), a clinical-stage macrophage reprogramming immunotherapy company, reported the poster presentation of a substantial survival benefit of AllocetraTM combined with immune checkpoint inhibition in a preclinical mesothelioma study at the International Society of Cell and Gene Therapy Annual 2022 Meeting (Press release, Enlivex Therapeutics, MAY 9, 2022, View Source [SID1234613905]). The poster was titled, "Allocetra-OTS, an Early Apoptotic Cellular Therapy Synergize with Chimeric Antigen Receptor (CAR) T Cell Therapy or Immune Check Point Inhibitor Against Peritoneal Solid Tumor."

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Mesothelioma, Treatment Landscape, and Macrophage-Solid Tumor Dynamics

Mesothelioma is one of the deadliest solid cancers with few treatment options, all of which have limited efficacy. People who are most at risk to develop mesothelioma generally have had long-term exposure to asbestos (e.g., construction workers, pipe fitters, and shipyard workers). It takes many years for mesothelioma to develop; it can appear 30 years after asbestos exposure. Immune checkpoint inhibitors targeting CTLA4 and PD1 are FDA-approved as first-line treatments for patients with unresectable malignant pleural mesothelioma.

In mesothelioma and in some other solid cancers, tumor cells, as part of their defense mechanisms, facilitate the recruitment of macrophages which become "pro-tumor" tumor associated macrophages (TAMs) rather than "anti-tumor" macrophages. The TAMs typically form a physical layer on top of the solid tumor, and induce immunosuppression in the solid tumor microenvironment. This in-turn promotes tumor growth and metastasis and makes it very difficult for the immune system or any anti-cancer drug to efficiently attack the cancerous cells. Allocetra is a cell therapy in development that is targeted at these TAMs, and its proposed mechanism of action is to change the balance of macrophage populations to skew towards anti-tumor macrophages and away from pro-tumor macrophages.

The Mesothelioma Model

To test the potential effect of cell therapy-induced macrophage reprogramming on difficult-to-treat solid tumors, Enlivex ran preclinical studies in which five groups of mice were implanted with mesothelioma cancer cells. The difference between the groups was the treatment given, which started on day 12 after the cancer’s initial growth period.

Results from multiple studies strongly support the potential of AllocetraTM to assist in the process of macrophage reprogramming in the solid tumor microenvironment and significantly change survival outcomes. As expected, only 1/16 (6%) of the untreated mice remained alive at day 42 (that one last remaining mouse died on day 65), compared with up to 25% survival for the mice in the group that was treated with the anti-CTLA4 immune checkpoint inhibitor. Surprisingly, AllocetraTM as a stand-alone treatment provided comparable survival rates as anti-CTLA4 monotherapy, with a 28.5% survival rate and a delayed cancer growth rate observed. Notably, the synergistic effect of treating with both drugs resulted in up to 100% survival with complete disappearance of the cancer. The effect was correlated with the AllocetraTM treatment dose. A lower dose of AllocetraTM provided slightly lower survival and cancer complete remission rates (67% complete remission for the low-dose treatment vs. up to 100% for the higher dose). The following chart provides a visual guide to the progressions/regression of the mesothelioma cancer in the different groups, as recorded for study mesothelioma AB12 137:

Across multiple studies of the AB12 mesothelioma model, anti-CTLA4 therapy significantly improved survival duration from mean 34±9 to 44.9 ±20 days (p<0.05). Allocetra as a stand-alone therapy improved survival duration to 52.3 ±20 days (p<0.02). The synergistic effect of the combination therapy of anti-CTLA4 + AllocetraTM improved survival duration to 86.7±20 days (p<0.0001) with complete cancer remission in 60-100% of mice, depending on the dose administered.

Prof. Dror Mevorach, Chief Scientific Officer of Enlivex, stated: "This reproducible and statistically significant data strongly support Allocetra’s proposed therapeutic mechanism of action of reprogramming macrophages in solid tumors. We believe that, in contrast to CAR-T, CAR-NK and other anti-cancer cell therapies directed at tumor antigens, AllocetraTM restores macrophage homeostasis in the tumor environment via reprogramming of pro-tumor macrophages. This may ultimately allow immune checkpoint inhibitors to be exponentially more effective."

Oren Hershkovitz, Ph.D., CEO of Enlivex, added: "Based on these results, Enlivex is planning to initiate a series of clinical trials during 2022 that are designed to evaluate Allocetra in combination with FDA-approved immune checkpoint inhibitor therapies in patients with advanced-stage solid tumors. To date, we have infused AllocetraTM in dozens of hospitalized patients in fragile condition resulting from sepsis and COVID-19-related organ dysfunction. We believe that the proposed differentiated mechanism of action of AllocetraTM, together with the safety and tolerability it has demonstrated in these prior studies, as well as the encouraging efficacy results of our preclinical solid tumor models, highlight an intriguing opportunity for Enlivex to provide another layer of life-saving therapy for patients who have few available options."

ABOUT ALLOCETRA

Allocetra is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as "unmet medical needs", as a stand-alone therapy or in combination with leading therapeutic agents.

On May 9, 2022 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported that it has entered into a definitive agreement with a single leading healthcare investor for the purchase and sale of 10,563,380 of the Company’s American Depositary Shares ("ADSs") (or ADS equivalents), each ADS representing ten (10) ordinary shares, at a purchase price of $1.42 per ADS (or ADS equivalent), in a registered direct offering (Press release, RedHill Biopharma, MAY 9, 2022, View Source [SID1234613885]). RedHill has also agreed to issue to the investor unregistered private warrants to purchase up to an aggregate of 13,204,225 ADSs in a concurrent private placement. The warrants have an exercise price of $1.48 per ADS, are exercisable six months after the issuance date and have a term of five and one-half years. The closing of the offering is expected to occur on or about May 11, 2022, subject to the satisfaction of customary closing conditions.

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Cantor Fitzgerald & Co. is acting as the exclusive placement agent for the offering.

The gross proceeds to the Company from this offering are expected to be approximately $15 million, before deducting the placement agent’s fees and other offering expenses payable by the Company. The Company intends to use the net proceeds from this offering for working capital, acquisitions, and general corporate purposes.

The securities described above (but not the warrants or the ADSs underlying the warrants) are being offered by the Company pursuant to a "shelf" registration statement on Form F-3 (File No 333-258259) previously filed with the Securities and Exchange Commission (the "SEC") on July 29, 2021, and declared effective by the SEC on August 9, 2021. The offering of the securities is made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A final prospectus supplement and accompanying prospectus relating to the securities being offered will be filed with the SEC. Electronic copies of the final prospectus supplement and accompanying prospectus may be obtained, when available, on the SEC’s website at View Source or by contacting Cantor Fitzgerald & Co., 499 Park Avenue, 4th Floor, New York, New York 10022, Attn: Capital Markets Department, or by email at [email protected].

The warrants described above were offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and Regulation D promulgated thereunder and, along with the ADSs underlying the warrants, have not been registered under the Act, or applicable state securities laws. Accordingly, the warrants and underlying ADSs may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Act and such applicable state securities laws.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.