On June 29, 2022 M.S.Q. Ventures ("MSQ") reported that its client, BioLineRx Ltd. ("BioLineRx") (NASDAQ/TASE: BLRX), has successfully entered into a co-development agreement with GenFleet Therapeutics, Inc., an immuno-oncology focused biopharmaceutical company based in Shanghai, China, for the development of Motixafortide in pancreatic ductal adenocarcinoma ("PDAC") (Press release, BioLineRx, JUN 29, 2022, View Source [SID1234616362]).

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Under the terms of the agreement, GenFleet will design and execute a randomized Phase 2b clinical trial that will enroll approximately 200 first-line metastatic PDAC patients in China. This randomized controlled study will aim to evaluate the superiority of Motixafortide in combination with an anti-PD-1 and chemotherapy compared to chemotherapy alone, the current standard of care.

"This collaboration is based on the highly encouraging results from our Phase 2a COMBAT/KEYNOTE-202 study of Motixafortide in combination with an anti-PD-1 and chemotherapy, which provide strong support for continued development in this very challenging disease. With its broad solid tumor oncology pipeline and highly experienced development team, we believe we have found an outstanding partner in GenFleet to execute a rigorously designed randomized Phase 2b trial," said Philip Serlin, CEO of BioLineRx. "The MSQ team helped to navigate through the complexity of cross-border transactions and secured this transaction by deploying their deep knowledge of the global market. We are highly impressed with MSQ’s "thinking outside the box" approach and their expertise in deal structuring and negotiation."

"The results of the COMBAT/KEYNOTE-202 Phase 2a study demonstrate the benefit of combining the CXCR4 inhibitor Motixafortide with an anti-PD-1 and chemotherapy in a second-line setting," said Qiang Lu, Chairman of GenFleet. "We believe that this combination could be beneficial to patients in a first-line setting as well, and we hope to confirm this in a randomized trial. We are thrilled to be partners with BioLineRx in the development of this late-stage clinical asset, and look forward to initiating this important trial as quickly as possible. Throughout this journey, MSQ team has demonstrated professionalism and dedication in helping both of our teams to reach the finish line in a timely fashion."

Echo Hindle-Yang, CEO of MSQ, reflects on the transaction, "This collaboration demonstrates another excellent example of global co-development, which leverages each company’s regional expertise to accelerate the development of new treatments. We are excited to see the alliance between BioLineRx and Genfleet to pursue the treatment of PDAC, which has proven to be incredibly challenging. I am impressed by Phil’s commitment to developing Motixafortide in PDAC which is also shared by GenFleet’s Dr. Lu. With such a strong commitment from each team, we believe that patients will benefit from this collaboration. We are honored to move forward with this cross-border partnership, and help achieve future success.

On June 29, 2022 ADC Therapeutics SA (NYSE: ADCT) reported the first patient has been dosed in LOTIS-7, a Phase 1b clinical trial evaluating ZYNLONTA in combination with other anti-cancer agents in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (Press release, ADC Therapeutics, JUN 29, 2022, View Source [SID1234616379]).

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"As ZYNLONTA has been shown in preclinical studies to have synergistic or additive effects when combined with other anti-cancer therapies, we are eager to explore the potential of our differentiated CD19-directed ADC in combination with other established therapies," said Joseph Camardo, MD, Chief Medical Officer of ADC Therapeutics. "We are excited by the opportunity to allow more lymphoma patients to achieve a response and benefit from the new combinations we are evaluating in LOTIS-7."

The first arm of the LOTIS-7 open-label, multi-center, multi-arm Phase 1b trial will evaluate the safety and activity of ZYNLONTA in combination with polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, high grade B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, and Burkitt lymphoma. The trial will include multiple arms in two parts – a dose escalation part and a dose expansion part. For more information about the LOTIS-7 trial, please visit www.clinicaltrials.gov (identifier NCT04970901).

ZYNLONTA is also being evaluated in the LOTIS clinical trial program as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy. For more information about the LOTIS trials, please visit View Source

About ZYNLONTA (loncastuximab tesirine-lpyl)

ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death.

The U.S. Food and Drug Administration (FDA) has approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ZYNLONTA is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.

On June 29, 2022 Codiak BioSciences, Inc. (NASDAQ: CDAK), a clinical-stage biopharmaceutical company pioneering the development of exosome-based therapeutics as a new class of medicines, reported the initiation of patient dosing in its Phase 1 clinical trial of exoASO-STAT6, an engineered exosome precision medicine candidate designed to selectively deliver antisense oligonucleotides to disrupt STAT6 signaling in tumor associated macrophages (TAMs) and induce an anti-tumor immune response (Press release, Codiak Biosciences, JUN 29, 2022, View Source [SID1234616363]). exoASO-STAT6 is Codiak’s third clinical program and the first to evaluate a systemically administered exosome-based drug candidate .

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"Targeting macrophages is the next great frontier in cancer immunotherapy and we are encouraged by the monotherapy anti-tumor activity exhibited by exoASO-STAT6 in preclinical models, which has not been observed among other approaches to date. We believe this may indicate the potential to bring transformative treatments to patients facing intractable forms of cancer," said Douglas E. Williams, Ph.D., CEO, Codiak. "The initiation of this trial is also a significant milestone for our company, as the advancement of exoASO-STAT6 into the clinic highlights the versatility of our engineering platform. This candidate is the first of our programs to target macrophages, the first to carry a nucleic acid and the first to be administered intravenously."

The Phase 1 clinical trial will evaluate the safety, tolerability, biomarkers and preliminary anti-tumor activity of exoASO-STAT6 in patients with advanced hepatocellular carcinoma (HCC), patients with liver metastases from primary gastric cancer and colorectal cancer (CRC). The study is anticipated to enroll patients across four cohorts at sequentially escalating dose levels, with subjects in the initial cohorts receiving biweekly exoASO-STAT6 administered intravenously over the course of 28 days. Ultimately the trial may enroll up to 30 patients. Initial Phase 1 data are expected in the first half of 2023.

TAMs promote tumor growth by exhibiting an immune suppressive M2 phenotype. Reprogramming TAMs toward a pro-inflammatory M1 phenotype may be a compelling approach to induce anti-tumor immunity. The M2 phenotype is controlled by key transcription factors such as STAT6, which have proven difficult to drug selectively in TAMs using prior approaches. Codiak plans to initially develop exoASO-STAT6 for primary cancers of the liver, where STAT6 expression has been correlated with poor survival.

In multiple in vivo preclinical studies, exoASO-STAT6 demonstrated potent single agent activity, including >90% tumor growth inhibition and 50-80% complete responses. In HCC models, exoASO-STAT6 induced significant knockdown of STAT6 mRNA, attenuated tumor growth and induced complete remission of tumor lesions in 50% of mice. This anti-tumor activity was enhanced (75% complete remissions) when exoASO-STAT6 was administered with anti-PD1 antibodies. The monotherapy activity was accompanied by remodeling of the tumor microenvironment including significant expansion of M1-like macrophages and induction of an adaptive anti-tumor immune response, enabling tumor elimination.

About the engEx Platform

Codiak’s proprietary engEx Platform is designed to enable the development of engineered exosome therapeutics for a wide spectrum of diseases and to manufacture them reproducibly and at scale to pharmaceutical standards. By leveraging the inherent biology, function and tolerability profile of exosomes, Codiak is developing engEx exosomes designed to carry and protect potent drug molecules, provide selective delivery and elicit the desired pharmacology at the desired tissue and cellular sites. Through its engEx Platform, Codiak seeks to direct tropism and distribution by engineering exosomes to carry on their surface specific targeting drug moieties, such as proteins, antibodies/fragments, and peptides, individually or in combination. Codiak scientists have identified two exosomal proteins that serve as surface and luminal scaffolds. By engineering the exosome surface or lumen and optimizing the route of administration, Codiak aims to deliver engEx exosomes to the desired cell and tissue to more selectively engage the drug target, potentially enhancing the therapeutic index by improving potency and reducing toxicity.

On June 29, 2022 Fuzionaire Diagnostics, Inc. ("Fuzionaire Dx") reported a collaborative research agreement with McMaster University ("McMaster") under which theranostic radiopharmaceuticals developed with Fuzionaire Dx’s HetSiFA platform will be evaluated at McMaster’s comprehensive preclinical nuclear medicine facilities (Press release, Fuzionaire Diagnostics, JUN 29, 2022, View Source [SID1234616380]).

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The collaboration expands Fuzionaire Dx’s capabilities to evaluate oncologic theranostics made from its HetSiFA platform. The collaboration will begin with the biological and preclinical evaluation of multiple theranostic candidates targeting an undisclosed type of cancer and selection of promising candidates for further development.

Fuzionaire Dx creates theranostic candidates by combining its HetSiFAs, or heteroaromatic silicon-fluoride acceptors, with cancer-targeting peptides and other ligands. With the HetSiFA library, new theranostic candidates are created within weeks. The HetSiFA platform is compatible with fluorine-18, the leading radionuclide used in positron-emission-tomography (PET) imaging, and leading alpha- and beta-emitting radionuclides used for therapy, providing unique flexibility in creating new candidates.

Theranostics is a term that describes a "see it, treat it" approach to cancer that uses one radioactive drug to reveal tumor locations and a second radioactive drug to deliver therapy that kills cancer cells.

Primary leadership for the scientific collaboration includes Christopher Waldmann, PhD, Chief Scientific Officer of Fuzionaire Dx, and Saman Sadeghi, PhD, Associate Professor, Chemistry & Chemical Biology, and Principal Investigator, Radiochemistry & Radiopharmaceuticals, at McMaster University.

On June 29, 2022, Seres Therapeutics, Inc. (the "Company") reported that entered into a Securities Purchase Agreement with certain institutional accredited investors (the "IAIs") named therein (the "Non-Affiliate Purchase Agreement") and a Securities Purchase Agreement with certain directors and officers of the Company (the "Affiliates", and collectively with the IAIs, the "Purchasers") named therein (the "Affiliate Purchase Agreement" and, together with the Non-Affiliate Purchase Agreement, the "Purchase Agreements") (Filing, 8-K, Seres Therapeutics, JUN 29, 2022, View Source [SID1234616399]). Pursuant to the Purchase Agreements, the Company agreed to issue and sell in a registered direct offering (the "Offering") (i) an aggregate of 31,238,094 shares of the Company’s common stock, par value $0.001 per share (the "Common Stock"), at a purchase price of $3.15 per share (the "Purchase Price") to the IAIs, for aggregate gross proceeds to the Company of $98.4 million, and (ii) an aggregate of 507,936 shares of Common Stock at the Purchase Price to the Affiliates, for aggregate gross proceeds to the Company of $1.6 million, in each case pursuant to an effective shelf registration statement on Form S-3, as amended (File No. 333-244401) and a related prospectus supplement filed with the Securities and Exchange Commission. The closing of the Offering is expected to occur on or about July 5, 2022, subject to the satisfaction of customary closing conditions.

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The Company expects to receive net proceeds from the Offering of approximately $96.8 million, after deducting the placement agent’s fees and estimated offering expenses payable by the Company. The Company intends to use the net proceeds from the Offering for commercial readiness and manufacture of SER-109 for the U.S. market, including expanding longer-term commercial manufacturing capacity, advancing the clinical development of SER-109 for the EU market, and other general corporate and working capital purposes. The Company believes that its existing cash, cash equivalents and investments, together with the net proceeds from the Offering, will fund its operations for at least 12 months from the date of the prospectus related to the Offering filed with the Securities and Exchange Commission (the "SEC") on June 30, 2022. This evaluation does not take into consideration contingent payments associated with SER-109 FDA approval, which the Company anticipates in the first half of 2023, as these are uncertain and there is no assurance the Company will receive them. These contingent payments include the potential to receive a $125 million milestone payment pursuant to the Company’s collaboration and license agreement with NHSc Pharma Partners upon SER-109 FDA approval and a $25 million tranche under its existing term loan with Hercules Capital, Inc., which becomes available upon the satisfaction of certain conditions, including FDA approval of SER-109.

The Purchase Agreements contain customary representations, warranties and agreements by the Company, customary conditions to closing, indemnification obligations of the Company and the Purchasers, including for liabilities under the Securities Act of 1933, as amended (the "Securities Act"), other obligations of the parties and termination provisions.

The foregoing description of the Purchase Agreements is not complete and is qualified in its entirety by reference to the full text of the Non-Affiliate Purchase Agreement and Affiliate Purchase Agreement, forms of which are filed as Exhibits 10.1 and 10.2, respectively, to this Current Report on Form 8-K and are incorporated by reference herein.