On November 20, 2022 Elpiscience Biopharmaceuticals, Inc. ("Elpiscience"), a clinical-stage biopharmaceutical company focused on developing next-generation immunotherapies to benefit cancer patients worldwide, reported positive studies for its innovative immunotherapeutic molecules at the SITC (Free SITC Whitepaper) 2022 Annual Meeting, including anti-SIRPα monoclonal antibody ES004, PD-L1/SIRPα bispecific antibody ES019, anti-LILRB2 monoclonal antibody ES009, anti-SIGLEC15 antibody ES012, and anti-LAG3 monoclonal antibody ES005 (Press release, Elpiscience, NOV 20, 2022, View Source [SID1234624262]).

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Study highlights:

1. Title: Treatment of anti-SIRPα in combination with anti-TAA exerts superior anti-tumor activity
Abstract No.: 793

SIRPα is an inhibitory receptor expressed mainly on myeloid cells and dendritic cells. Ligation of CD47 to SIRPα delivers a "don’t eat me" signal to suppress macrophage phagocytosis. Tumor cells frequently overexpress CD47 to evade macrophage-mediated destruction. Anti-SIRPα mAb ES004 potently potentiates antibody dependent cellular phagocytosis (ADCP) activity of antibodies against tumor associated antigens (TAAs) in vitro and in vivo.

Highlights:

ES004 recognizes pan-allele human SIRPα with high affinity
ES004 binds to a unique epitope on the CD47 binding domain of SIRPα
ES004 potently blocks CD47-SIRPα interaction and CD47 induced SIRPα signaling
ES004 effectively potentiates pan-allelic macrophage phagocytosis of tumor cells
ES004 has no negative impact on T cell activation
ES004 enhances anti-tumor activity in combination with anti-Claudin18.2 in MC38/hCLDN18.2 syngenetic tumor model
ES004 has demonstrated favorable PK, full target occupancy and excellent safety profile in cynomolgus monkeys.
2. Title: Dual targeting of innate and adaptive immune checkpoints with a PD-L1/SIRPα bispecific macrophage engager to promote anti-tumor activity
Abstract No.: 1211

The anti-PDL1/SIRPα bispecific antibody ES019, designed for tumor cell and immune cell dual targeting, is capable of reactivating macrophages and T cells to kill cancer cells with the potential to overcome the limitations of traditional anti-PD1 therapies and has demonstrated significantly enhanced tumor therapeutic efficacy and specificity versus combo or monotherapies.

Highlights:

ES019 phagocytosis activity is corrected with PD-L1 level on tumor cells
ES019 leads to better phagocytosis capability of tumor cells by M2-like than M1-like macrophage
ES019 activates T cells without induction of phagocytosis of T cells
ES019 shows favorable PK in mouse model
ES019 demonstrates single agent anti-tumor efficacy in animal model
3. Title: ES009, a LILRB2-specific blocking antibody, reprograms myeloid cells into pro-inflammation phenotype and potentiates T cell activation
Abstract No.: 1062

LILRB2 is predominantly expressed in myeloid lineage cells. Human LILRB2 broadly binds to multiple ligands and contributes to immune suppression in the tumor microenvironment (TME). Anti-LILRB2 mAb ES009 has demonstrated superior effects in converting immunosuppressive myeloid cells into pro-inflammation phenotypes in in vitro and ex vivo models.

Highlights:

ES009 specifically binds human LILRB2 with high affinity
ES009 binds to a unique epitope on D1 domain of LILRB2
ES009 potently blocks LILRB2 binding to multiple ligands
ES009 promotes monocytes and monocytes derived DCs into a pro-inflammatory status
ES009 effectively reprograms human monocyte derived M2 macrophages into pro-inflammation M1 phenotypes
ES009 effectively relives T cells from M2 macrophages mediated suppression
ES009 converts primary macrophages in malignant ascites in ovarian cancer patients into a pro-inflammatory status
4. Title: SIGLEC15 induces monocyte apoptosis and an SIGLEC15 antibody ES012 reverses myeloid cells driven immunosuppression
Abstract No.: 1401

SIGLEC15 is a glycan-recognition proteins belonging to the SIGLEC family and is highly expressed on TAM and many tumor cells. It’s reported that SIGLEC15 inhibits T cell activity via its binding to an unknown receptor on T cells. Elpiscience has identified a novel function of SIGLEC15 that SIGLEC15 can induce monocyte apoptosis and its inhibitory effect on T cell function is indirect. Based on this newly discovered SIGLEC15 biology, we have developed a potent, functional anti-SIGLEC15 mAb ES012 that has great potential to reverse immune suppression in TME to promote anti-tumor immunity.

Highlight:

SIGLEC15 induces monocyte apoptosis, which is dependent on sialic acid binding and mediated via caspase-3
SIGLEC15 inhibits T cell function via myeloid cells but not by directly binding to T cells
ES012 is a high affinity anti-SIGLEC15 monoclonal antibody.
ES012 can rescue monocyte apoptosis and inhibit T cells by SIGLEC15.
ES012 showed superior anti-tumor efficacy and better PK profile than benchmark antibody in preclinical model
5. Title: ES005, a high affinity anti-LAG3 monoclonal antibody, inhibits the interactions between LAG3 and multiple ligands and enhances anti-tumor activity of T cells in preclinical models
Abstract No.: 426

LAG3 plays an important role in regulating immune homeostasis with multiple biological activities related to T cell functions. Anti-LAG3 mAb ES005 has demonstrated significant tumor growth inhibition in in vivo mouse tumor models, and showed excellent PK and safety profile in NHPs, indicating great potential to be used as next-generation immune checkpoint inhibitor in cancer treatment.

Highlights:

ES005 is a high affinity and cynomolgus reactive anti-LAG3 mAb
ES005 binds to a unique epitope on LAG3 D1 domain
ES005 potently blocks LAG3 binding to multiple ligands including FGL-1
ES005 effectively upregulates NFAT reporter gene transcription via blocking LAG3/MHC-II interaction
ES005 effectively reverses LAG3 driven inhibition of T cell activation
ES005 monotherapy potently inhibits tumor growth in EMT6 syngeneic tumor model
ES005 was well tolerated in cynomolgus monkeys with favorable PK Profile

On November 18, 2022 Palisade Bio, Inc. (Nasdaq: PALI), a clinical stage biopharmaceutical company advancing therapies for acute and chronic gastrointestinal (GI) complications, reported the appointment of Herbert B. Slade, MD, FAAAAI as Chief Medical Officer of Palisade Bio (Press release, Seneca Biopharma, NOV 18, 2022, View Source [SID1234624398]).

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Dr. Slade is a proven medical and regulatory professional with over 25 years of leadership experience in the pharmaceutical and medical device industries. Over the course of his career, he has demonstrated execution of regulatory negotiations with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) and the design, conduct and reporting of clinical programs.

"Over the past six months Dr. Slade has provided important input and guidance in advancing the development of LB1148 as a clinical advisor to the Company. We firmly believe his appointment as Chief Medical Officer will be a natural transition, and we are very pleased to welcome him to the executive leadership team. Throughout his career, he has amassed valuable expertise across the healthcare industry and academia and has developed a deep-rooted, respected skillset in research and development that we believe will be critical as we move our development programs forward. We will continue to leverage Dr. Slade’s perspective and leadership as we work to unlock the full potential of the Company and LB1148 for all stakeholders," commented JD Finley, interim CEO of Palisade Bio.

"There remains a significant unmet need when it comes to addressing acute and chronic gastrointestinal post-surgical complications and the serious risks that come with them. I believe that the demonstrated mechanism to protect intestinal barrier health and the data seen to date well position LB1148 to become a potential standard of care, and I am dedicated to further advancing its development. With the prioritization on the prevention of adhesions program, I believe we have the potential to offer millions of patients an important therapeutic option and provide a much-needed benefit. Having closely worked with the Palisade Bio team as a clinical advisor for LB1148 over the past several months, I am excited to continue building on the progress made and look forward to bringing its development successfully across the finish line," added Dr. Slade.

Dr. Slade currently serves as the Adjunct Clinical Associate Professor, Dept. of Pediatrics, Texas College of Osteopathic Medicine, UNTHSC and as Treasurer and member of the Board of Directors of The Wound Healing Society. He joins Palisade Bio having most recently served as the President and Managing Director of Chisholm Clinical Research Services, LLC (CCRS) where he provided assistance with clinical testing and development of promising new products for 11 client companies in seven countries. Prior to CCRS, Dr. Slade served as Chief Scientific and Medical Officer, Advanced Wound Management of Smith and Nephew plc before transitioning to Sr. Vice President, Research & Development where he was responsible for restructuring three strategic business unit R&D departments and two clinical groups into a single worldwide R&D organization, adding post-marketing surveillance. Prior to that he served as Chief Medical Officer and Senior Vice President at DFB Pharmaceuticals until it was acquired by Smith & Nephew in 2012. Additional career appointments include Chief Medical Officer of 3M Pharmaceuticals where he was responsible for all Medical, Clinical Research, Biometrics, Data Management and Pharmacovigilance personnel worldwide for 12 years. Dr. Slade also was afforded the unique opportunity to work at Rhône-Poulenc Rorer (RPR) with the prestigious Dr. Jonas Salk, as the principal physician and clinical immunologist on the Salk HIV Immunogen project. During that time, he assisted Dr. Salk on a wide range of program issues including the scientific validity of a therapeutic vaccine (now termed Theracines or Pharmacines), and the importance of the Th1/Th2 concept.

Dr. Slade has authored or co-authored over 100 publications. He has held academic positions at a number of universities including University of Michigan Medical School, Cornell University Medical College, University of North Texas Health Science Center, and University of Pennsylvania Medical School. Dr. Slade received his undergraduate degree in biology from Hamilton College and his M.D. from State University of New York Upstate Medical University in Syracuse, New York. He completed post doctorate work at S.U.N.Y. Upstate Medical Center and C.S. Mott Children’s Hospital and completed his fellowship at the University of Michigan.

On November 18, 2022 Shanghai Fosun Pharma reported it has licensed US rights to a PD-1 candidate from its longstanding partner, Henlius Biotech, in an $840 million agreement (Press release, Fosun Pharma, NOV 18, 2022, View Source [SID1234624259]). Although Fosun is Henlius’s controlling shareholder, Henlius declared it was looking for a US partner as recently as three months ago. Despite their relationship, Henlius negotiated an enviable contract with Fosun, consisting of a $140 million upfront payment, a one-time $50 million regulatory milestone payment and up to $650 million in sales milestones, plus royalties. The PD-1, serplulimab, was the thirteenth PD-1/L1 inhibitor approved in China

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On November 18, 2022, 2seventy bio, Inc. (the "Company") reported that entered into a Sales Agreement (the "Sales Agreement") with Cowen and Company, LLC ("Cowen") to sell shares of the Company’s common stock, par value $0.0001 per share (the "Common Stock"), having an aggregate offering price of up to $150,000,000 (the "Placement Shares"), from time to time during the term of the Sales Agreement, through an "at the market" equity offering program under which Cowen will act as the Company’s sales agent (Filing, 8-K, 2seventy bio, NOV 18, 2022, View Source [SID1234624258]).

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Under the Sales Agreement, the Company will set the parameters for the sale of the Placement Shares, including the number of Placement Shares to be issued, the time period during which sales are requested to be made, any limitation on the number of Placement Shares that may be sold in any one trading day and any minimum price below which sales may not be made. Subject to the terms and conditions of the Sales Agreement, Cowen may sell the Placement Shares by methods deemed to be an "at the market offering" as defined in Rule 415 promulgated under the Securities Act of 1933, as amended, including, without limitation, sales made through The Nasdaq Global Select Market ("Nasdaq"), on any other existing trading market for the Common Stock. In addition, if expressly authorized by the Company, Cowen may also sell shares in privately negotiated transactions. In conducting such sales activities, Cowen will use its commercially reasonable efforts consistent with its normal trading and sales practices and applicable state and federal laws, rules and regulations and the rules of Nasdaq. The Company has no obligation to make any sales of Common Stock under the Sales Agreement, and the Sales Agreement may be suspended or terminated by the Company upon prior notice to Cowen or by Cowen upon prior notice to the Company, or at any time under certain circumstances, including, but not limited to, the occurrence of a material adverse change in the Company.
The Company will pay Cowen a commission equal to up to three percent (3.0%) of the gross sales proceeds of any Placement Shares sold through Cowen under the Sales Agreement, and also has provided Cowen with customary indemnification rights.

Any sales of Placement Shares under the Sales Agreement will be made pursuant to the Company’s shelf registration statement on Form S-3 (File No. 333-268222) filed with the Securities and Exchange Commission (the "Commission") on November 7, 2022 and declared effective on November 18, 2022. The Company filed a prospectus supplement with the Commission on November 18, 2022 in connection with the offer and sale of the Placement Shares pursuant to the Sales Agreement.
The foregoing description of the material terms of the Sales Agreement is qualified in its entirety by reference to the full agreement, a copy of which is filed as Exhibit 1.1 to this Current Report on Form 8-K and is incorporated herein by reference.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of any offer to buy the securities discussed herein, nor shall there be any offer, solicitation or sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

On November 18, 2022, Genprex, Inc. (the "Company") reported that entered into an Equity Distribution Agreement (the "Agreement") with JMP Securities LLC, serving as agent (the "Agent") with respect to an at-the-market offering program under which the Company may offer and sell, from time to time at its sole discretion, shares of its common stock, par value $0.001 per share (the "Common Stock"), having an aggregate offering price of up to $50.0 million (the "Shares") through the Placement Agent (the "Offering") (Filing, 8-K, Genprex, NOV 18, 2022, View Source [SID1234624257]). Any Shares offered and sold in the Offering will be issued pursuant to the Company’s Registration Statement on Form S-3 filed with the Securities and Exchange Commission (the "SEC") on June 12, 2020, as amended on July 1, 2020, which was declared effective on July 17, 2020, the prospectus supplement relating to the Offering filed with the SEC on November 18, 2022 and any applicable additional prospectus supplements related to the Offering that form a part of the Registration Statement. A copy of the opinion of Lowenstein Sandler LLP relating to the legality of the issuance and sale of the Shares is attached as Exhibit 5.1 hereto.

The Agent may sell the Shares by any method permitted by law deemed to be an "at the market offering" as defined in Rule 415 of the Securities Act of 1933, as amended, including, without limitation, sales made through The Nasdaq Capital Market ("Nasdaq") or on any other existing trading market for the Common Stock. The Agent will use commercially reasonable efforts to sell the Shares from time to time consistent with its normal sales practices and applicable federal rules, regulations and Nasdaq rules, based upon instructions from the Company (including any price, time or size limits or other customary parameters or conditions the Company may impose). The Company will pay the Agent a commission equal to three percent (3%) of the gross sales proceeds of any Shares sold through the Agent under the Agreement, and also has provided the Agent with customary indemnification and contribution rights.

The Agent is not required to sell any specific number or dollar amount of securities, but will use commercially reasonable efforts to sell, on behalf of the Company, all of the shares of common stock requested to be sold by the Company, consistent with its normal trading and sales practices, on mutually agreed terms between the Agent and the Company. There is no arrangement for funds to be received in any escrow, trust or similar arrangement.

The foregoing description of the Agreement is not complete and is qualified in its entirety by reference to the full text of the Agreement, a copy of which is filed herewith as Exhibit 1.1 to this Current Report on Form 8-K and is incorporated herein by reference. A copy of the opinion of Lowenstein Sandler LLP relating to the legality of the issuance and sale of the shares in the Offering is attached as Exhibit 5.1 hereto.

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