GlycoMimetics Announces Initiation of Clinical Trial Evaluating Uproleselan in Combination With Venetoclax and Azacitidine

On July 12, 2021 GlycoMimetics, Inc. (Nasdaq: GLYC) reported that clinicians at University of California (UC) Davis Comprehensive Cancer Center initiated dosing of the first patient in a clinical study of uproleselan combined with venetoclax and azacitidine for the treatment of older or unfit patients with treatment-naïve acute myeloid leukemia (AML). Brian A. Jonas, MD, PhD, FACP, UC Davis Division of Hematology/Oncology, is the clinical trial’s principal investigator (Press release, GlycoMimetics, JUL 12, 2021, View Source [SID1234584780]).

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!

According to Eric Feldman, MD, GlycoMimetics’ Chief Medical Officer, "While the field has seen strong uptake on venetoclax paired with a hypomethylating agent (HMA) in the frontline unfit AML setting, the depth and durability of responses, particularly in patients with adverse risk biology, has been somewhat less than optimal. In this setting, there remains a significant unmet need, and we know that environment-mediated drug resistance (EMDR), driven by E-selectin, contributes to HMA/venetoclax resistance. If the study shows that E-selectin antagonism with uproleselan improves minimal residual disease (MRD) negative response rates, this would be an important step forward that underscores the foundational opportunities for uproleselan across the broad spectrum of patients treated for AML."

The UC Davis Comprehensive Cancer Center study is an investigator-sponsored trial (IST) for which GlycoMimetics is providing uproleselan. Designed to evaluate the safety and efficacy of the triple combination, the study is non-randomized, open label and multi-center. The goal of the two-part trial is first to determine a recommended Phase 2 dose, and then to explore efficacy in a dose expansion cohort. Up to 31 patients will be enrolled, and a preliminary/interim readout is expected in 2022.

At the 2020 annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), a preclinical study of uproleselan in combination with venetoclax and the HMA azacitidine demonstrated the triple combination’s potential in overcoming some of the limitations related to depth and durability of response with venetoclax/HMA alone. An oral presentation highlighted how antagonizing E-selectin with uproleselan can overcome microenvironment-mediated resistance to venetoclax/HMA therapy. In the study, the addition of uproleselan both prolonged survival of the murine model, and also promoted normal hematopeoic stem cell pro-survival signaling.

About Uproleselan

Discovered and developed by GlycoMimetics, uproleselan is an investigational, first-in-class, targeted antagonist of E-selectin. Uproleselan (yoo’ pro le’ sel an), currently in a comprehensive Phase 3 development program in AML, has received Breakthrough Therapy designation from the U.S. FDA and the Chinese Health authority for the treatment of adult AML patients with relapsed or refractory disease. Uproleselan is designed to block E-selectin (an adhesion molecule on cells in the bone marrow) from binding with blood cancer cells as a targeted approach to disrupting well-established mechanisms of leukemic cell resistance.

Imago BioSciences, Inc. Announces Proposed Initial Public Offering of Common Stock

On July 12, 2021 Imago BioSciences, Inc. ("Imago"), a clinical stage biopharmaceutical company discovering new medicines for the treatment of myeloproliferative neoplasms (MPNs), reported that it has commenced an underwritten initial public offering of up to 7,000,000 shares of its common stock (Press release, Imago BioSciences, JUL 12, 2021, View Source [SID1234584797]). All of the shares to be sold in the offering will be offered by Imago. In addition, Imago expects to grant the underwriters for the offering a 30-day option to purchase up to an additional 1,050,000 shares of common stock at the public offering price, less underwriting discounts and commissions. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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!

Imago currently expects to use the net proceeds from this offering to fund the clinical development of bomedemstat for essential thrombocythemia through the completion of both the ongoing Phase 2 clinical trial and the planned Phase 3 clinical trial, clinical development of bomedemstat for myelofibrosis through the completion of both the ongoing and planned Phase 2 clinical trials, cGMP process development for bomedemstat, development of bomedemstat for additional indications, and for the development of additional pipeline candidates, internal research, and any remaining amounts for working capital and general corporate purposes.

Jefferies, Cowen, Stifel and Guggenheim Securities are acting as joint book-running managers for the offering.

A registration statement relating to the securities has been filed with the Securities and Exchange Commission, but has not yet become effective. These securities may not be sold, nor may offers be accepted, prior to the time the registration statement becomes effective. This press release shall not constitute an offer to sell or the solicitation of an offer to buy, 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 of these securities under the securities laws of any such state or jurisdiction.

In addition to the shares being sold in the initial public offering, Imago has agreed to sell an additional $20 million of its common stock in a concurrent private placement at the public offering price per share to Pfizer Inc. The sale of these shares of common stock will not be registered under the Securities Act of 1933, as amended, and will be subject to a 180-day lock-up agreement. The concurrent private placement is also scheduled to close concurrent with the initial public offering, subject to satisfaction of customary closing conditions. The closing of Imago’s initial public offering is not conditioned upon the closing of the concurrent private placement, but the closing of the concurrent private placement is conditioned upon the closing of the initial public offering.

The offering of these securities is being made only by means of a prospectus, copies of which may be obtained from: Jefferies LLC, 520 Madison Avenue, 2nd Floor, New York, NY 10022, or by email at [email protected] or by phone at 877-821-7388; or Cowen and Company, LLC, c/o Broadridge Financial Solutions, Attn: Prospectus Department, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at (833) 297-2926 or by email at [email protected]; or Stifel, Nicolaus & Company, Incorporated, Attention: Syndicate, One Montgomery Street, Suite 3700, San Francisco, CA 94104, or by telephone at (415) 364-2720, or by email at [email protected]; or Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, NY 10017, by telephone at (212) 518-9544 or by email at [email protected].

Imago has applied to list its common stock on The Nasdaq Global Select Market under the symbol "IMGO."

Biogen and Innocare Announce License and Collaboration Agreement For Orelabrutinib, an Innovative CNS Penetrant BTK Inhibitor For the Potential Treatment of Multiple Sclerosis

On July 12, 2021 Biogen Inc. (Nasdaq: BIIB) and InnoCare Pharma Limited (HKEX: 09969) reported that they have entered into a license and collaboration agreement for orelabrutinib, an oral small molecule Bruton’s tyrosine kinase inhibitor (BTKi) for the potential treatment of multiple sclerosis (MS) (Press release, Biogen, JUL 12, 2021, View Source [SID1234584816]). Orelabrutinib is a covalent BTKi with high selectivity and the ability to cross the blood-brain barrier, and is currently being studied in a multi-country, placebo-controlled Phase 2 trial in relapsing-remitting MS.

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!

Orelabrutinib inhibits BTK, which is a key enzyme that is part of the signaling cascade of immune cells including B cells and myeloid cells. With the ability to cross the blood brain barrier, orelabrutinib has the potential to inhibit B cell and myeloid cell effector functions in the central nervous system (CNS), and may provide a clinically meaningful benefit on progression in all forms of MS. By addressing the progressive biology of the disease, orelabrutinib may offer people living with MS an additional treatment option and the possibility to slow disease progression.

"Given the complex and chronic nature of MS, we believe the unique characteristics of orelabrutinib, combining high selectivity and CNS penetrance, may translate to potential clinical advantages relative to other BTKi programs," said Alfred Sandrock, Jr., M.D., Ph.D., Head of Research and Development at Biogen. "For over 30 years, Biogen has led in MS research and today has a leading portfolio of MS products. We are focused on developing next-generation approaches that we hope will improve outcomes for those living with progressive and relapsing forms of MS."

"Biogen is a recognized leader in neuroscience and we believe this transaction will help advance the development of orelabrutinib in MS," said Jasmine Cui, Ph.D., Co-Founder, Chairwoman and Chief Executive Officer at InnoCare. "We are excited about the potential of orelabrutinib for the treatment of patients with all forms of MS given the potential efficacy and safety profile, plus a promising level of blood-brain barrier penetration. BTK inhibitors may have the potential to transform the treatment paradigm of autoimmune diseases, in particular MS."

Under the terms of the agreement, Biogen will have exclusive rights to orelabrutinib in the field of MS worldwide and certain autoimmune diseases outside of China (including Hong Kong, Macau and Taiwan), while InnoCare will retain exclusive worldwide rights to orelabrutinib in the field of oncology and certain autoimmune diseases in China (including Hong Kong, Macau and Taiwan). InnoCare will receive a $125 million upfront payment and is eligible to receive up to $812.5 million in potential development milestones and potential commercial payments should the collaboration achieve certain development, commercial milestones and sales thresholds. InnoCare is also eligible to receive tiered royalties in the low to high teens on potential future net sales of any product resulting from the collaboration. Closing of the collaboration is contingent on completion of review under antitrust laws, including the Hart-Scott-Rodino (HSR) Antitrust Improvements Act of 1976 in the U.S., and other customary closing conditions.

About Orelabrutinib
Orelabrutinib is a small molecule Bruton’s tyrosine kinase inhibitor (BTKi) developed for the treatment of cancer and in development for the potential treatment of autoimmune diseases.

In the field of multiple sclerosis, orelabrutinib is a BTKi with high selectivity and ability to cross the blood-brain barrier and could achieve high-target occupancy in the central nervous system. It is currently being investigated in a global Phase 2 study in RRMS patients.

In the field of oncology, InnoCare received approval for orelabrutinib from the China National Medical Products Administration (NMPA) in two indications: the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL)/small lymphocytic lymphoma (R/R SLL), and the treatment of patients with relapsed/refractory mantle cell lymphoma (R/R MCL).

About Bruton’s Tyrosine Kinase Inhibitors
Bruton’s tyrosine kinase (BTK) is a tyrosine kinase that is encoded by the BTK gene in humans. BTK plays a crucial role in B-cell receptor signaling cascade in B cells leading to B cell proliferation, survival, differentiation and cytokine production. BTK also plays a key function in myeloid cell signaling. Central nervous system (CNS) penetrant BTK small molecule inhibitors work by inhibiting B cells and myeloid cells in the periphery and in the CNS. Among myeloid cells expressing BTK, microglia, which reside in the CNS, have been shown to express high level of BTK in multiple sclerosis.

48Hour Discovery and RayzeBio Announce Strategic Research Collaboration

On July 12, 2021 48Hour Discovery Inc and RayzeBio reported the companies have entered a strategic research collaboration to discover and develop novel peptide-based radiopharmaceuticals for the treatment of cancer (Press release, 48Hour Discovery, JUL 12, 2021, View Source [SID1234586901]).

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!

"We are excited to work with a cutting edge biotechnology company like RayzeBio" said Ratmir Derda, CEO of 48Hour Discovery "For this collaboration project, 48Hour Discovery will identify potent ligands for a series of targets selected by RayzeBio. This project will help us further validate the potential of our billion-scale molecular libraries and cloud-based discovery pipeline. We are looking forward to accelerating the preclinical programs of RayzeBio and providing peptide drug candidates that will advance the radiopharmaceutical field."

"48Hour Discovery has a promising proprietary platform for novel peptide discovery," said Ken Song, M.D., CEO of RayzeBio. "We are intrigued by the potential to quickly discover novel binders."

Under the terms of the agreement, 48HD will receive undisclosed payments. RayzeBio has exclusive rights to develop and commercialize peptides discovered under the collaboration, and an option to further expand the collaboration to include additional targets.

Alpha Tau & Healthcare Capital Corp. to Combine and Create A $1-Billion Publicly Traded Company

On July 11, 2021 Alpha Tau reported that proprietary Alpha DaRT is designed to deliver uniquely potent alpha radiation to destroy solid tumors with localized precision, sparing surrounding healthy tissue, thereby maintaining cancer patients’ quality of life (Press release, Alpha Tau Medical, JUL 11, 2021, View Source [SID1234584768]). Alpha DaRT has recently received FDA’s Breakthrough Device Designation for the indication of Squamous Cell Carcinoma of the skin and oral cavity without curative standard of care, and preclinical studies support evaluation across various cancer indications (skin, pancreas, breast and GBM, among others).

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!

– The transaction represents an implied pro forma equity value of approximately $1 billion and is expected to provide up to $367 million in gross proceeds, including up to $275 million of cash held in the trust account of Healthcare Capital Corp. (Nasdaq: HCCC) and a $92 million PIPE.

– The $92 million fully-committed PIPE is anchored by a combination of Healthcare-focused financial and strategic investors including Yozma Investment Co. (part of Yozma Group Korea), Grand Decade Developments (an affiliate of China Grand Pharmaceutical and Healthcare Holdings), as well as other leading technology investors including OurCrowd, Regah Ventures and the co-founders of Apax Partners, Alan Patricof and Sir Ronald Cohen. Medison Group, an early supporter of Alpha Tau and global pharma company that provides access to highly innovative therapies to patients in international markets, is also an investor in the PIPE.

– After giving effect to the transaction (and assuming no redemptions by public shareholders), Alpha Tau is expected to have approximately $362 million of cash on the balance sheet.

– Net proceeds are to be used for further expansion of Alpha Tau’s clinical strategy including the pursuit of FDA marketing authorization, a broad array of R&D activities, expanding manufacturing capacity and preparing for commercialization, and are expected to provide cash runway at least into 2024.

– All Alpha Tau shareholders will retain 100% of their equity holdings in the public company.

– Alpha Tau will continue to be led by its current management team, and upon closing, it is expected that HCC Chairman Dr. David M. Milch will be appointed to the Alpha Tau Board of Directors.

– The proposed business combination is expected to be completed by the end of 2021, upon which Alpha Tau is expected to be listed on Nasdaq.

JERUSALEM and WILMINGTON, Del., July 8, 2021 /PRNewswire/ — Alpha Tau Medical Limited ("Alpha Tau"), the developer of the pioneering alpha-radiation cancer therapy Alpha DaRT, and Healthcare Capital Corp. ("HCC") (Nasdaq: HCCC), a special purpose acquisition company, reported they have entered into a definitive business combination agreement (the "Business Combination"). Upon closing of the Business Combination, Alpha Tau is expected to be listed on the Nasdaq.

Alpha Tau’s proprietary Alpha DaRT (Diffusing Alpha-emitters Radiation Therapy) enables highly potent and conformal alpha-irradiation of solid tumors through the intra-tumoral insertion of radium-224 impregnated sources mainly affecting the tumor, sparing the healthy tissue around it. In the company’s first-in-human clinical trial for Squamous Cell Carcinoma ("SCC") tumors of the skin & oral cavity exhibited 100% overall response rate and approximately 78% complete response rate. In June 2021, Alpha Tau received FDA Breakthrough Device Designation for the use of Alpha DaRT in the treatment of SCC of the skin and oral cavity without curative standard of care.

Alpha Tau has developed a robust clinical trial strategy with leading global centers, including its flagship US multi-center feasibility study currently ongoing, led at Memorial Sloan Kettering Cancer Center in New York, which recently enrolled its first patient.

A group of Healthcare-focused financial and strategic investors have committed to participate in the transaction through a fully committed ordinary share PIPE of approximately $92 million at $10.00 per share. Investors in the PIPE include Yozma Investment Co. (part of Yozma Group Korea) and Grand Decade Developments (an affiliate of China Grand Pharmaceutical and Healthcare Holdings) as well as other leading technology investors including OurCrowd, Regah Ventures and the co-founders of Apax Partners, Alan Patricof and Sir Ronald Cohen. Medison Group, an early supporter of Alpha Tau and global pharma company that provides access to highly innovative therapies to patients in international markets, is also an investor in the PIPE.

"Following the recent enrollment of the first patient in our flagship US feasibility study and receipt of FDA Breakthrough Device Designation, this transaction represents another significant milestone on Alpha Tau’s journey to transform the treatment of solid tumors through the precision delivery of alpha radiation. We are grateful to the outstanding team at HCC, whose cadre of experienced and well-regarded professionals have provided superb execution and continued support for Alpha Tau, and we are excited for Dr. David M. Milch to join as our newest member of the Board of Directors upon the closing of the business combination. We thank our investors, both new joiners as well as those who have supported us for years, who continue to demonstrate their faith in the company and its leadership," said Uzi Sofer, CEO and Chairman of Alpha Tau.

"The completion of this transaction will allow the company to realize its vision and implement the clinical development plans and construction of our manufacturing plants around the world, in order to bring hope to millions of patients around the world."

"This transaction ensures that we are well capitalized to accelerate our ambitious plans across multiple fronts," said Raphi Levy, CFO of Alpha Tau. "We look forward to delivering continued clinical momentum and hope for patients as we evolve into a public company."

"We are excited about Alpha Tau’s unique therapy, which has generated a response observed across a wide array of solid tumors in pre-clinical studies, with minimal side effects, positioning it to potentially become a vital weapon in the battle against cancer," said Dr. David M. Milch. "After evaluating many opportunities in the healthcare industry, we believe that Alpha Tau stands out as the best choice for a business combination due to its proprietary technology, rapid clinical and product development and easy to administer treatment solution for the great number of cancer patients worldwide."

"It was a pleasure to work with the team at HCC as their due diligence advisor following my departure as Commissioner of the FDA in January 2021," said Dr. Stephen M. Hahn. "My background as a medical and radiation oncologist helped me immediately appreciate the potential of Alpha Tau’s therapy in providing a solution for a potentially significant number of patients, including those with untreatable or difficult to treat tumors, whether alone or in combination with other therapies such as immunotherapies. I would expect the product to be well received by the clinical community because of the potential applications, modest side effect profile, and demonstrated potency of the Alpha DaRT"

Proceeds of the business combination and the PIPE will be primarily used to:

advance ongoing, and launch, new clinical trials;

continue existing, and initiate additional, clinical and research collaborations;

develop and expand global manufacturing capacity;

develop KOL centers of excellence; and

prepare for commercialization efforts.

Key Transaction Terms

The Business Combination values Alpha Tau at an implied pre-money equity value of $600 million, and is expected to add approximately $337 million of cash to its balance sheet upon closing, inclusive of $275 million in HCC’s trust (assuming no redemptions by public shareholders) and $92 million in PIPE proceeds, net of transaction expenses.

All existing Alpha Tau shareholders will retain 100% of their current equity holdings and are expected to hold approximately 59% of the pro forma company immediately following the closing. Following the closing of the business combination, Alpha Tau is expected to be listed on the Nasdaq.

The Business Combination was unanimously approved by each of Alpha Tau’s and HCC’s Boards of Directors, and HCC Chairman Dr. David M. Milch is expected to join the Board of Directors after closing. The transaction is expected to be completed by the end of 2021, and is subject to obtaining necessary regulatory approvals, the fulfillment of customary closing conditions, as well as the approval of both Alpha Tau’s and HCC’s shareholders.

Additional information about the proposed business combination, including a copy of the definitive agreement and investor presentation, will be provided in a Current Report on Form 8-K to be filed by HCC with the Securities and Exchange Commission and available at www.sec.gov.

Advisors

Citigroup is acting as financial advisor to Alpha Tau. Citigroup, Piper Sandler, and Cantor Fitzgerald are acting as joint placement agents on the PIPE. Cantor Fitzgerald is acting as a capital markets advisor to HCC. Value Base M&A Ltd. is also acting as financial advisor on the transaction.

Latham & Watkins LLP and Meitar | Law Offices are acting as legal advisors to Alpha Tau. Ellenoff Grossman & Schole LLP and FBC & Co. are acting as legal advisors to HCC. Winston & Strawn LLP is acting as legal advisor to the placement agents.

Management Presentation

A link to a presentation by management of Alpha Tau and HCC discussing the business and the proposed transaction can be found at www.netroadshow.com/nrs/home/#!/?show=d422ce03

The investor presentation is being filed by Alpha Tau and HCC with the Securities and Exchange Commission ("SEC") and will be available on the SEC’s website at www.sec.gov.