On December 27, 2020 ONK Therapeutics Ltd, an innovative natural killer (NK) cell therapy company, reported that it has secured three new exclusive option license agreements which strengthen its off-the-shelf, dual-targeted natural killer (NK) cell therapy platform and extend its pre-clinical pipeline to four programs across both hematological and solid tumors (Press release, ONK Therapeutics, DEC 17, 2020, View Source [SID1234572992]).

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The first option agreement, with Cellerant Therapeutics, gives exclusive rights to a humanized CLEC12A scFv binder. CLEC12A is strongly expressed by blasts in the majority of AML patients. The option to license has enabled ONK to expand its pre-clinical product portfolio, launching a fourth program (ONKT104). This dual-targeted approach combines the CLEC12A CAR with a TNF-related apoptosis-inducing ligand variant (TRAILv) targeting death receptor 4 (DR4).

"While expressed on leukemic stem cells, CLEC12A is absent from normal hematopoietic stem cells and we thus expect that our dual-targeted NK cell therapy approach should enable safe targeting, with a reduced risk of prolonged aplasia in AML," said Prof Michael O’Dwyer MD, ONK Therapeutics’ co-founder, and CSO.

The second agreement in-licenses a humanized, tumor-specific antibody targeting an aberrantly glycosylated tumor-associated form of MUC1 (TA-MUC1) from Glycotope GmbH. Multiple solid tumor types express the mucin MUC1, including non-small cell lung cancer, breast cancer, and ovarian cancer. This antibody will be integrated into ONK’s pre-clinical program ONKT103, for solid tumors.

Non-selective targeting of MUC1 could be problematic since the target is also expressed by healthy tissues, but O’Dwyer explains how ONK’s dual-targeted approach can be used to address this. "We have designed a CAR tailored to the glycosylation pattern distinct to tumor-associated MUC1 with specific recognition of the carbohydrate antigens Tn and T on MUC1, the expression of which is restricted to cancer cells. Glycotope has identified the glycosylation pattern as a way to unlock the potential of TA-MUC1 as a solid tumor target. ONK is thus set to bring the natural benefits of NK cells over T cells to bear on TA-MUC1, in a tumor-specific fashion, while also further boosting efficacy and countering resistance through the use of our TRAIL variant targeting DR5," he said.

ONK’s unique platform approach combines the expression of a chimeric antigen receptor (CAR) and a high affinity, membrane-bound TRAILv. The incorporation of these two humanized scFvs has the potential to minimize the risk of immunogenicity in the allogeneic setting.

ONK is also exploring several innovative strategies to improve the homing of NK cells. This is an important consideration as ex-vivo expansion can lead to changes in chemokine receptor expression. Through this new license agreement with the NIH, ONK plans to enforce the expression of CCR7, which is downregulated on NK cell expansion. This may improve the homing of NK cells to lymph nodes and is expected to be particularly useful for ONK’s off-the-shelf CD19 program targeting B cell lymphoma, ONKT101, which is partnered with Avectas.

ONK is making rapid progress since it announced its most recent financing in October. Chris Nowers, ex Kite Pharma Head of Europe, who joined at that time as Chief Executive Officer, said: "The recent American Society of Hematology (ASH) (Free ASH Whitepaper) meeting highlighted the NK cell therapy area as offering great hope as the next generation of advanced cell therapies. We believe our best-in-class off-the-shelf, dual-targeted NK cell therapy platform has the potential to improve performance and overcome some of the shortcomings seen with earlier approaches. These new licensing activities strengthen and expand our programs and illustrate our ambition and strategy to become a leader in this exciting field."

The company recently expanded its operations into the USA, moving into JLABS @ San Diego, Johnson & Johnson Innovation’s flagship facility, at the heart of San Diego’s precision medicine and cell therapy cluster. This represents a second facility that complements its main R&D team and operations in Galway, Ireland. The company’s recruitment drive across both facilities has been rapid and the company continues to expand its capability in key areas, including NK cell biology, construct design, gene editing, and process development.

On December 17, 2020 SCYNEXIS, Inc. (Nasdaq:SCYX) reported the pricing of its underwritten public offering of common stock, pre-funded warrants and warrants (Press release, Scynexis, DEC 17, 2020, View Source [SID1234572991]). The shares and warrants are being sold at a public offering price of $6.25 per share and accompanying warrants, and the pre-funded warrants are being sold at a public offering price of $6.249 per pre-funded warrant and accompanying warrants. The gross offering proceeds to SCYNEXIS from this offering are expected to be approximately $85.0 million, before deducting the underwriting discount and other estimated offering expenses, and excluding the exercise of any pre-funded warrants or warrants. All of the shares of common stock, pre-funded warrants and warrants are being offered by SCYNEXIS.

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At closing, SCYNEXIS will issue 8,390,000 shares of its common stock and, pre-funded warrants to purchase 5,210,000 shares of common stock, and two series of warrants to purchase an aggregate of 13,600,000 additional shares of its common stock. The pre-funded warrants will be issued to certain purchasers who have elected to purchase them in lieu of shares of common stock in this offering, as those purchasers would otherwise have exceeded 19.99% (or such lesser percentage as required by the investor) beneficial ownership of our common stock immediately following the offering. The shares of common stock, pre-funded warrants and warrants will be issued separately. The Series 1 warrants to purchase up to 6,800,000 shares of common stock have a one-year term and an exercise price of $7.33 per share, and the Series 2 warrants to purchase up to 6,800,000 shares of common stock have a three-and-a-half-year term and an exercise price of $8.25 per share. The pre-funded warrants and the warrants in each series are exercisable immediately upon issuance. The warrants will be certified, and will be delivered to the investors by physical delivery following the closing. There is no established public trading market for the pre-funded warrants or the warrants, and SCYNEXIS does not expect a market to develop.

Guggenheim Securities, LLC and Cantor Fitzgerald & Co. are serving as joint book-running managers for the offering. Ladenburg Thalmann & Co. Inc. and National Securities Corporation, a wholly owned subsidiary of National Holdings, Inc. (NASDAQ: NHLD), are serving as co-lead managers for the offering. Brookline Capital Markets, a division of Arcadia Securities, LLC, and WBB Securities LLC are serving as co-managers for the offering.

A shelf registration statement relating to the securities being sold in this offering was filed with the U.S. Securities and Exchange Commission (the "SEC") on September 11, 2020, and was declared effective on October 1, 2020. The offering will be made only by means of a preliminary and final prospectus supplement and accompanying prospectus. When available, copies of the preliminary and final prospectus supplements and accompanying prospectus relating to the proposed public offering may be obtained by contacting: Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison, 8th Floor, New York, NY 10017, or by telephone at (212) 518-9658, or by email to [email protected]; or Cantor Fitzgerald & Co., Attn: Capital Markets, 499 Park Avenue, 6th floor, New York, NY 10022; mail: [email protected]. The final terms of the offering will be disclosed in the final prospectus supplement to be filed with the SEC.

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

In connection with the offering SCYNEXIS terminated its Controlled Equity OfferingSM Sales Agreements with Cantor Fitzgerald & Co. and Ladenburg Thalmann & Co. Inc.

On December 17, 2020, Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported the submission of a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) for AYVAKIT (avapritinib) for the treatment of adult patients with advanced systemic mastocytosis (SM) (Press release, Blueprint Medicines, DEC 17, 2020, View Source [SID1234572990]). AYVAKIT is a potent and selective inhibitor of D816V mutant KIT, the primary driver of SM, and is being developed to treat advanced and non-advanced forms of the disease.

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Blueprint Medicines requested priority review for this application, which, if granted, could result in a six-month review process. The FDA has a 60-day filing review period to determine whether the sNDA is complete and acceptable for filing. The FDA granted breakthrough therapy designation to AYVAKIT for the treatment of advanced SM, including the subtypes of aggressive SM, SM with an associated hematological neoplasm and mast cell leukemia.

"Today’s submission is an important step toward our goal of bringing AYVAKIT to patients with advanced systemic mastocytosis, a debilitating and life-threatening rare disease," said Fouad Namouni, M.D., President, Research & Development. "Our application is based on an unprecedented clinical dataset in this disease, which showed that patients receiving AYVAKIT had high overall response and complete remission rates, with prolonged survival, and the treatment was generally well-tolerated. We look forward to working closely with the FDA during the review, as we seek to introduce the first precision therapy targeting the underlying cause of systemic mastocytosis."

About SM

SM is a rare disease driven by the KIT D816V mutation. Uncontrolled proliferation and activation of mast cells result in chronic, severe and often unpredictable symptoms for patients across the spectrum of SM. The vast majority of those affected have non-advanced (indolent or smoldering) SM, with debilitating symptoms that lead to a profound, negative impact on quality of life. A minority of patients have advanced SM, which encompasses a group of high-risk SM subtypes including aggressive SM, SM with an associated hematological neoplasm and mast cell leukemia. In addition to mast cell activation symptoms, advanced SM is associated with organ damage due to mast cell infiltration and poor overall survival.

Debilitating symptoms, including anaphylaxis, maculopapular rash, pruritis, diarrhea, brain fog, fatigue and bone pain, often persist across all forms of SM despite treatment with a number of symptomatic therapies. Patients often live in fear of severe, unexpected symptoms, have limited ability to work or perform daily activities, or isolate themselves to protect against unpredictable triggers. Currently, there are no approved therapies for the treatment of SM that selectively inhibit D816V mutant KIT.

About AYVAKIT (avapritinib)

AYVAKIT (avapritinib) is a kinase inhibitor approved by the FDA for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. For more information, visit www.AYVAKIT.com. This medicine is approved in Europe under the brand name AYVAKYT for the treatment of adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation.

AYVAKIT/AYVAKYT is not approved for the treatment of any other indication, including SM, in the U.S. by the FDA or in Europe by the European Commission, or for any indication in any other jurisdiction by any other health authority.

Blueprint Medicines is developing AYVAKIT globally for the treatment of advanced and indolent SM.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of AYVAKIT in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for AYVAKIT in the rest of the world.

On December 17, 2020 Merus N.V. (Nasdaq: MRUS), a clinical-stage oncology company developing innovative, full-length multi-specific antibodies (Biclonics and TriclonicsTM), and Sema4, a patient-centered health intelligence company, reported they have entered into a strategic agreement to utilize Sema4’s advanced genomic testing to identify patients with tumors harboring neuregulin 1 gene (NRG1) fusions who may be eligible for investigational treatment with the bispecific antibody Zenocutuzumab ("Zeno") in the Phase 1/2 eNRGy trial sponsored by Merus (Press release, Merus, DEC 17, 2020, View Source [SID1234572989]).

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Under the terms of the agreement, Sema4 will perform genomic testing to identify patients with advanced NRG1 positive (NGR1+) solid tumors who might need novel clinical options and raise awareness of Merus’ eNRGy trial.

NRG1 gene fusions are a group of rare genomic alterations emerging as a potential actionable driver of tumorigenesis and growth across many types of solid tumors, including lung, breast, pancreatic, ovarian, and colorectal cancers. Zeno, through its unique mechanism of blocking the interaction of the NRG1 fusion protein with its receptor HER3, has the potential to be particularly effective against NRG1+ cancers.

"Our next-generation genomic testing solutions deliver critical information to oncologists and their patients, enabling them to make informed treatment decisions," said Eric Schadt, PhD, Founder and Chief Executive Officer of Sema4. "We are pleased to partner with the Merus team to provide clinicians with this advanced molecular analysis of solid tumors, and to increase awareness about emerging investigational care options and patient eligibility for the eNRGy trial."

"Our agreement with Sema4, and the opportunity to leverage advanced genomic testing solutions for oncology, hold promise to help us accelerate enrollment in our eNRGy clinical trial," said Dr. Andrew Joe, Chief Medical Officer of Merus. "We look forward to continuing to explore the potential for Zeno to become an effective new treatment option for patients with cancers harboring NRG1 fusions."

Merus is currently enrolling patients into the Phase 1/2 eNRGy trial to assess the safety and anti-tumor activity of Zeno monotherapy in NRG1+ cancers. The eNRGy trial consists of three cohorts: NRG1+ pancreatic cancer; NRG1+ non-small cell lung cancer; and NRG1+ other solid tumors.

On December 17, 2020 Lantern Pharma (Nasdaq: LTRN), a clinical-stage biopharma company using its proprietary RADR artificial intelligence ("A.I.") platform to transform cancer drug development and identify patients who will benefit from its targeted oncology therapeutics, reported a collaboration and research agreement with the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center and Kennedy Krieger Institute (Press release, Lantern Pharma, DEC 17, 2020, View Source [SID1234572987]). The collaboration will focus on the further development of Lantern’s LP-184 in glioblastoma multiforme (GBM). Based in Baltimore, Johns Hopkins is a leading research center for brain cancers and one of the largest brain tumor treatment and research centers in the world with a focus on treating an extremely large number of patients affected by all types of brain tumors.

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The collaboration will focus on advancing the targeted use of LP-184 in defined subtypes of GBM and clarifying the most promising clinical applications for the drug candidate. The goal of the collaboration is to develop a clinically ready program that has characterized the drug candidate with the most biologically relevant and robust genomic or biomarker signature. By having a gene signature that can be used in identifying patients that have the potential for the highest response, Lantern can potentially accelerate future clinical trials and shorten the time to achieving patient benefit for GBM patients.

The research program is at the forefront of translational cancer medicine and will use patient-derived cancer cells that are studied using physiologically relevant in vitro and in vivo models. This innovative approach allows researchers to more precisely understand the biology of what actually happens inside the cancer tumor, which will more accurately establish the precise biomarker signatures and help provide data-driven insight into additional mechanisms that can be leveraged in the fight against brain cancer.

"Collaborations with world-leading cancer centers are an essential part of our strategy to rapidly advance the insights driving our therapeutic programs and grow the power of our RADR A.I. platform by adding millions of new, unique, and proprietary data points in areas of high unmet need in cancer," said Panna Sharma, CEO of Lantern Pharma. "This relationship with Johns Hopkins is expected to allow us to use state-of-the-art models and biological methods to add more physiologically relevant data and insights into the mechanisms of LP-184, and further shape our algorithms for how our drug candidates interact with specific brain cancer subtypes. We believe the unique insights we gain will equip Lantern with critical advantages in our aim of accelerating LP-184’s path to clinical trials and ultimately commercialization while saving millions of dollars in development costs. This data-enabled and biomarker-based approach has the potential to meaningfully bend the cost curve of cancer drug development and help bring personalized cancer therapies to patients with reduced economic burden, and greater efficacy."

The research will be led by John Laterra, MD, Ph.D., an internationally recognized researcher in neurology, oncology, and neuroscience. Dr. Laterra serves as the Co-Director of the Brain Cancer Program and the Director of the Division of Neuro-Oncology at Johns Hopkins School of Medicine where he specializes in investigating mechanisms of brain tumor malignancy, tumor vascular biology, and identification of new therapeutic targets in gliomas.

LP-184 is a DNA-damaging small molecule drug candidate currently in preclinical development for certain genomically defined solid tumors, including glioblastomas. As a next-generation alkylating agent that preferentially damages DNA in cancer cells that overexpress certain biomarkers and can cross the blood-brain barrier, we believe LP-184 has the potential to be used as both monotherapy as well as a synergistic agent in combination with other drugs.

"We are focused on finding how LP-184 can exploit certain molecular mechanisms in gliomas to offer improved disease management and survival for glioblastoma patients," said Dr. Kishor Bhatia, Chief Scientific Officer at Lantern Pharma. Dr. Bhatia continued, "We look forward to our collaboration with Johns Hopkins, the Brain Cancer Program and Dr. Laterra who is at the forefront of GBM research. His approach combines real world patient insights along with advanced methodologies and patient-derived models that can improve the quality of the insight and provide more relevant data on efficacy. We look forward to sharing these results with the broader scientific and clinical community."

Among several objectives, the research goals are to determine whether certain genomic signatures generated with RADR, Lantern’s A.I. platform, can predict response to LP-184 and a more favorable outcome as compared to standard of care agents being used today. LP-184 has been advanced using Lantern’s proprietary RADR A.I. platform that leverages over one billion curated cancer data points, machine learning, genomics, and computational biology to accelerate the discovery of potential mechanisms of action, and biomarker signatures that correlate to drug response in cancer patients.

Although significant recent advances have been made in the use of targeted and biomarker-based therapies in cancer, GBM remains an area that has not experienced significant improvement in patient outcomes. The overall five-year survival rate for GBM across all stages remains at only 5.5% in the US, and GBM accounts for nearly 52% of all primary brain tumors each year according to the National Cancer Institute.