On March 22, 2021 ProMIS Neurosciences Inc. (TSX: PMN) (OTCQB: ARFXF), a biotechnology company focused on the discovery and development of antibody therapeutics targeting toxic oligomers implicated in the development of neurodegenerative diseases, reported that the completion of an US$7M (CDN$8.75M) private placement of convertible unsecured debentures (the "Debentures") (Press release, ProMIS Neurosciences, MAR 22, 2021, View Source [SID1234576949]).

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The investors include Mike Gordon of Fenway Sports Group, the Kraft Group, Henry McCance, co-founder of the Cure Alzheimer’s Fund, and Jeremy Sclar of WS Development Group. "After conducting diligence with a number of experts in the field, we are impressed with the tremendous potential of ProMIS Neurosciences and its unique platform of drug candidates to have a profound impact in the fight against Alzheimer’s and other neurodegenerative diseases. Our group is pleased to provide funding for the next phase of the company’s exciting future", stated Mike Gordon of Fenway Sports Group.

"We are honored to have the support of such a distinguished group of investors, all of whom are accomplished leaders in the business and life sciences arenas" said Gene Williams, ProMIS Executive Chairman.

Debenture Terms

The Debentures are convertible into ProMIS common shares at the option of the holder at a conversion price of US$0.10 per share and accrue interest at 1% per annum, which is payable annually. At the company’s election, accrued interest may be paid in cash or common shares (such number of shares determined by dividing the interest due by the 5-day volume-weighted average trading price or "VWAP" of the common shares).

The Debenture mature on March 22, 2026. Prior to the maturity date, the Company may force conversion of the Debentures at the conversion price upon raising US$50M in equity and/or debt cumulatively. On the maturity date, the Company may redeem the outstanding principal amount of the Debentures in either cash or common shares (at the then 5-day VWAP less a 10% discount) or a combination thereof at its election. Amounts redeemed in common shares on the Maturity Date will be subject to TSX acceptance.

The investors were granted a right to participate, on a pro rata basis, in subsequent company offerings of equity securities for cash consideration pursuant to a public offering or a private placement.

The Debentures and any common shares issued on conversion are subject to a four-month hold period that expires on July 22, 2021. Net proceeds will be used for working capital and general corporate purposes.

ProMIS plans to accelerate progress toward a number of top priorities, including:

Advancing the PMN310 monoclonal antibody, our potential "best in class" next generation Alzheimer’s treatment, into clinical testing;
Enhancing our partnering prospects for programs under active discussion by allowing us to invest in additional validation data;
Expanding our portfolio of products and intellectual property into new target areas, using our proprietary discovery platform;
Advancing our partnered diagnostic programs;
Achieving NASDAQ listing;
Expanding our Board of Directors; and
Expanding our management team, capitalizing on the talent pool in Boston, to support a growing and ambitious scope of activity.
Retirement of our CEO

Finally, a note of great appreciation for our CEO, Dr. Elliot Goldstein. Elliot, who just turned 70, has announced his intention to retire from a full time role by the end of 2021. Even though Elliot is irreplaceable, ProMIS has initiated a search for a new CEO to help us achieve our potential. "Elliot has been a close friend and valued business partner for decades," said Gene Williams, "without his significant contributions, we would not have been able to take ProMIS from just a great science idea to a company with a growing portfolio of therapies that have the potential to be life-altering for patients. On behalf of the entire ProMIS community, and patients who in the future may benefit from our therapies, I offer Elliot our sincere thanks and gratitude".

"ProMIS Neurosciences was launched six years ago based on a world class scientific platform from our CSO and scientific founder, Dr. Neil Cashman. Playing a key role in this endeavor has been one of the most challenging yet rewarding experiences of my 40 odd years in pharmaceutical drug development. I am delighted for this exciting new phase of the Company", stated Dr. Elliot Goldstein, ProMIS CEO.

On March 22, 2021 ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, reported the publication of preclinical data in the Journal for ImmunoTherapy of Cancer (JITC) highlighting efficacy of ImmunityBio’s PD-L1 t-haNK natural killer cell-based therapy in combination with T cell-based immunotherapy against heterogeneous tumors (Press release, NantKwest, MAR 22, 2021, View Source [SID1234576948]). ImmunityBio’s novel PD-L1 t-haNKs are derived from a human, allogeneic NK cell line (NK-92) that has been engineered to express IL-2, CD16, and a chimeric antigen receptor (CAR) that recognizes PD-L1.

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Human solid tumors are made of multiple clones of tumor cells, some of which harbor genomic alterations that make them invisible to T cells. These resistant clones accomplish this "cloaking ability" by preventing the presentation of the tumor antigens on MHC-I receptors, thus "hiding" from killer T cells. For these patients, maximum activation of T cells with immunotherapy is unlikely to lead to durable tumor control or a cure. However, when NK cells are activated, tumor recognition and targeting is restored. The study shows that when subpopulations of tumors cells escape T cell detection or killing, they upregulate PD-L1 in the process because of interferon in the tumor microenvironment. This increase in tumor cell PD-L1 expression sensitizes them to killing by PD-L1 t-haNKs.

"Our results suggest that sequential treatment, first with T cell immunotherapy to kill the sensitive tumor cells and upregulate PD-L1 on the remaining cells, followed by PD-L1 t-haNK treatment, may overcome the issue of tumor heterogeneity and enhance rates of durable tumor control in patients with relapsed solid cancers," said Clint T. Allen, M.D., Principal Investigator, Section on Translational Tumor Immunology in the National Institute on Deafness and Other Communication Disorders (NIH) and corresponding author of the publication.

The publication by first author Maxwell Lee et al., "Chimeric antigen receptor engineered NK cellular immunotherapy overcomes the selection of T cell escape variant cancer cells," describes the development of preclinical models with heterogenous cancers containing T cell escape variant tumor cells. T cell-based immunotherapy administered in these preclinical models resulted in IFNγ production that in turn upregulated PD-L1 expression in T cell escape variants. Subsequent administration of irradiated PD-L1 t-haNKs targeted and eliminated the tumor cell populations that had evolved to be resistant to T-cell immunotherapy alone, resulting in synergistic anti-tumor activity.

"We are excited to see this preclinical study that affirms our hypothesis of ‘Quantum Oncotherapeutics,’ which is currently being studied in Phase1/2 QUILT trials across multiple tumor types. The theory we hold is that our treatment itself induces changes in the tumor immune microenvironment. By anticipating these dynamic cellular changes, we can administer and activate NK cells at the optimal time and, ultimately, outsmart the tumor. These spatial-temporal insights informing treatment, have the potential to change the paradigm of cancer care with modernized immunotherapy protocols, beyond the standard-of-care therapy and beyond checkpoint therapy alone. Late-stage, randomized controlled trials in pancreatic and lung cancers that orchestrate NK cells and T cells are underway at ImmunityBio to confirm this hypothesis," said Patrick Soon-Shiong, M.D. Founder and Executive Chairman of ImmunityBio.

On March 22, 2021 Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) ("Sonnet" or the "Company"), a biopharmaceutical company developing innovative targeted biologic drugs, reported the appointment of Richard Kenney, M.D. as Chief Medical Officer and Manuel Dafonseca, as Head of Clinical Operations, effective March 22, 2021 (Press release, Sonnet BioTherapeutics, MAR 22, 2021, View Source [SID1234576945]).

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"I am pleased to welcome Richard and Manuel to Sonnet at such an exciting time as we prepare to enter SON-1010, our proprietary fully human Interleukin 12 (IL-12) therapeutic candidate configured with our Fully Human Albumin Binding (FHAB) technology, into the clinic," said Pankaj Mohan, Ph.D., Founder and CEO. "Richard is a seasoned industry leader with a demonstrated track record of overseeing clinical development teams and managing regulatory affairs. Manuel will bring to Sonnet his expertise in clinical operations and project management that comes at an opportune time as we continue to prepare our FHAB platform for its first clinical study."

Dr. Kenney has more than 20 years of experience in translational-stage development of biologics, as well as the commercialization strategy and corporate management of preclinical, clinical-stage and commercialized vaccines and immunotherapies. As President of ClinReg Biologics, he has provided strategic consulting in clinical and regulatory affairs of biologics, medical monitoring and pharmacovigilance in several capacities. Dr. Kenney most recently served as Chief Development Officer at X-VAX Technology and previously held Chief Medical Officer roles at Immune Design and Crucell Holland, where he led the clinical development and regulatory affairs groups. Dr. Kenney was a researcher/reviewer for the FDA for over six years and did post-graduate training at Duke and NIH. Dr. Kenney received a B.S. in Chemistry from George Washington University and his M.D. from Harvard Medical School.

"I am thrilled to join Sonnet to continue to build upon the important work of the team," commented Dr. Kenney. "I believe the FHAB platform has the potential to address difficult-to-treat solid tumors in broad cancer populations and at various stages of the disease. I look forward to applying my skillset as we advance our FHAB programs, as well as the low-dose IL-6 programs, through the clinic."

Mr. Dafonseca has over 30 years of experience in pharmaceutical development, ranging from discovery stage programs to post approval activities. Most recently he served as Director of Global Clinical Trial Operations – Oncology at Merck where he was responsible for the successful execution, enrollment and quality of his assigned portfolio within the company’s oncology portfolio. Prior to his time at Merck, Mr. Dafonseca served as the Director of Clinical Operations at Ipsen Biopharmaceuticals, where he led the North America clinical operations group, including the strategic planning, execution and management of Dysport and Somatuline to support global regulatory submissions. Mr. Dafonseca received his B.S in Medical Technology and M.S. in Zoology and Physiology from Rutgers University.

"This is a dynamic time for Sonnet’s FHAB platform, as the Company prepares its lead candidates for the clinic, and I am excited to be joining the team," stated Manuel Dafonseca. "The recent non-human primate (NHP) data is very encouraging and I look forward to applying my experiences in clinical trial management, from early stage to pre-approval activities, to bring Sonnet’s innovative treatments to cancer patients."

On March 22, 2021 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) reported that the Company has entered into a multi-RNA target alliance with Takeda Pharmaceutical Company Limited ("Takeda") with the goal to discover and develop RNA targeting small molecule therapeutics for highly attractive targets that are difficult to address via more conventional approaches (Press release, Evotec, MAR 22, 2021, View Source;announcements/press-releases/p/evotec-and-takeda-enter-strategic-rna-targeting-drug-discovery-and-development-alliance-6038 [SID1234576944]).

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Evotec and Takeda will jointly identify and develop small molecules targeting a range of RNA targets aligned with Takeda’s research and development areas. The collaboration will leverage Evotec’s extensive RNA targeting platform to optimally identify promising RNA sequences to target with small molecule ligands that can be developed into potentially first-in-class therapeutics.

Under the terms of the agreement, Evotec will receive significant research funding and will be eligible to receive discovery, pre-clinical, clinical, commercial and sales milestone payments of up to US$ 160 m per programme. Additionally, Evotec is entitled to tiered royalties on net sales of any products resulting from the collaboration.

Dr Cord Dohrmann, Chief Scientific Officer of Evotec, commented: "Many highly validated targets have proven to be intractable via conventional protein targeting approaches. For this reason, Evotec has been pioneering RNA targeting strategies and approaches for quite some time. We are very excited about the opportunity to collaborate with Takeda in this field as both companies share the vision to jointly develop small molecule therapeutics against high value RNA targets that will deliver long awaited therapeutics."

"Takeda recognizes targeting RNA with small molecules as a promising new modality that has tremendous potential for much needed medicines for patients through modulating historically undruggable targets", said Dr Larry Hamann, Head, Drug Discovery Sciences, Takeda. "We are excited to be working with Evotec and their impressive capabilities."

On March 22, 2021 Aura Biosciences, a clinical-stage oncology company developing a novel class of virus-like drug conjugate (VDC) therapies for multiple oncology indications, reported the closing of an oversubscribed $80 million financing (Press release, Aura Biosciences, MAR 22, 2021, View Source [SID1234576943]). The financing was led by Matrix Capital Management and Surveyor Capital (a Citadel company) with participation from new investors, including Rock Springs Capital, Adage Capital Management LP and Velosity Capital. Existing investors Medicxi, Advent Life Sciences, Lundbeckfonden Ventures, Arix Bioscience, Chiesi Ventures, Ysios Capital and Columbus Venture Partners also participated in the round.

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Aura intends to use the proceeds from this financing to advance the clinical development of its VDC technology platform, including the pivotal Phase 3 program for AU-011, the Company’s lead candidate in development for the first line treatment of choroidal melanoma, and ongoing research for additional programs in ocular oncology, as well as expanding the VDC technology into bladder cancer, the first non-ophthalmic solid tumor indication.

"Aura is pioneering the development of a new class of targeted therapies for life-threatening cancers with our novel VDC technology platform. This funding from a syndicate of distinguished investors enables us to advance AU-011 into a pivotal Phase 3 program for the first line treatment of choroidal melanoma, a rare, life- and vision-threatening form of cancer with no drugs approved. It also allows us to continue to expand the reach of our VDC technology in additional ocular oncology indications and in the treatment of solid tumors like bladder cancer where there is a high unmet medical need for better targeted therapies to treat early and reduce the incidence of metastasis," said Elisabet de los Pinos, Ph.D., Chief Executive Officer of Aura.

In connection with this financing, Karan Takhar, Senior Managing Director of Matrix Capital Management, will join Aura’s Board of Directors.

Mr. Takhar said, "Matrix believes in the long-term potential of Aura’s VDC technology to further strengthen the Company’s position as a leader in ocular oncology and beyond within other types of cancers in need of better treatment options. We look forward to supporting Aura’s leadership team through this next stage of pipeline growth and transition into late-stage development with the commencement of the AU-011 pivotal program."

About AU-011 (belzupacap sarotalocan)

AU-011 is a first-in-class virus-like drug conjugate (VDC) therapy in development for the first line treatment of choroidal melanoma. The virus-like component of the VDC selectively binds unique heparan sulphate proteoglycans (HSPGs) that are modified and overexpressed on the tumor cell surface of choroidal melanoma cells (and other tumors) and delivers a potent cytotoxic drug that is activated with infrared light. Upon activation with an ophthalmic laser, the cytotoxic drug rapidly and specifically disrupts the cell membrane of malignant melanoma cells with a pro-immunogenic cell death that is believed to activate the immune system generating long term anti-tumor immunity. The unique specificity of tumor binding by the VDC enables the preservation of key eye structures, which may allow for the potential of preserving patients’ vision and reducing other long-term complications of radiation treatment. The possibility of early treatment intervention and the activation of the immune system could lead to a reduction in the metastatic rate for patients with this life-threatening disease. AU-011 can be delivered using equipment commonly found in an ophthalmologist’s office and does not require a surgical procedure, pointing to a potentially less invasive, more convenient therapy for patients and physicians. AU-011 for the treatment of choroidal melanoma has been granted Orphan Drug and Fast Track designations by the U.S. Food and Drug Administration and is currently in Phase 2 clinical development.