Exacis Biotherapeutics Presents Data On Its Stealth Mrna-engineered Nk-cell Platform At American Society Of Gene & Cell Therapy Annual Meeting

On May 25, 2021 Exacis Biotherapeutics Inc., a development-stage immuno-oncology company working to democratize access to the most advanced and effective cancer treatments, reported that key data related to its engineered iPSC-derived NK-cell platform at the American Society of Gene & Cell Therapy 24th Annual Meeting (Press release, Exacis Biotherapeutics, MAY 25, 2021, View Source [SID1234580591]). These data include the successful generation of functional NK cells from iPSCs engineered to contain a biallelic knockout of a key MHC class I gene. Exacis’ cell engineering strategy is designed to allow its ExaNK cells to evade surveillance by the patient’s immune system, thus rendering the cells rejection resistant, or "stealth", to enable increased persistence in patients without genotoxic pre-conditioning.

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"These results demonstrate the precision and efficiency of two key components of our platform, the mRNA-mediated cell reprogramming and the mRNA gene editing technologies, including mRNA vectorization of our proprietary, targeted gene editing endonuclease," said James Pan, PhD, Head of Discovery and Development at Exacis. "Our virus-free and DNA-free approach to cell engineering allows us to develop engineered cell therapies with no risk of vector integration and the associated long term safety issues."

"The results we are seeing in the lab continue to reinforce our hypothesis that highly effective cell therapy products can be produced using methods to greatly reduce safety risks and streamline manufacturing. We continue to take steps toward our goal of expanding patient access to these life saving cell therapy products," stated Gregory Fiore MD, President and CEO of Exacis Biotherapeutics.

Presentation Highlights:

Digital Presentation: "High-Efficiency Generation of Biallelic Gene Knockout iPSC Lines Using mRNA Gene Editing"

Abstract Number: 768

Allogeneic cell therapies derived from gene-edited iPSCs are being developed to address challenges associated with donor-derived allogeneic cell therapies, including host immune rejection of allogeneic cells. While these challenges can theoretically be addressed through genetic engineering, performing the required biallelic editing of defined loci remains technically challenging with current gene-editing approaches. We demonstrate efficient and precise targeting of defined loci in iPSCs using a novel, mRNA-encoded gene-editing endonuclease. We show generation of iPSC lines containing biallelic knockouts of a key MHC class I gene with 50% efficiency using mRNA reprogrammed iPSCs and a novel mRNA encoded gene editing protein. Absence of off-target editing was confirmed by whole-genome sequencing of one of the engineered iPSC lines. The high efficiency and specificity of this process enabled the selection of an iPS cell line containing only the desired edits without the extensive screening often required with other gene-editing approaches. When differentiated into NK cells, the engineered cells showed enhanced tumor cell engagement and cytokine production in comparison to peripheral blood derived control NK cells. The engineered cells are being further developed as a rejection resistant cell

therapy platform onto which additional components, including chimeric antigen receptors (CARs) and activity-enhancing cytokines, can be added.

Regeneron Announces Investor Conference Presentations

On May 25, 2021 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that it will webcast management participation as follows (Press release, Regeneron, MAY 25, 2021, View Source [SID1234580589]):

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Bernstein’s 37th Annual Strategic Decisions Conference at 8:00 a.m. ET on Wednesday, June 2, 2021
Goldman Sachs 42nd Annual Global Healthcare Conference at 10:30 a.m. ET on Tuesday, June 8, 2021
BMO Biopharma Day at 8:00 a.m. ET on Tuesday, June 22, 2021
The sessions may be accessed from the "Investors & Media" page of Regeneron’s website at View Source Replays of the webcasts will be archived on the Company’s website for at least 30 days.

Clarus Therapeutics And HavaH Therapeutics Announce Licensing Agreement For Product To Treat Androgen-Dependent Inflammatory Breast Disease And Certain Forms Of Breast Cancer

On May 25, 2021 Clarus Therapeutics Inc. ("Clarus"), a pharmaceutical company dedicated to providing solutions to unmet medical needs by advancing androgen and metabolic therapies for men and women, and HavaH Therapeutics ("HavaH"), an Australia-based biopharmaceutical company developing androgen therapies for inflammatory breast disease and certain forms of breast cancer by using the innate breast-tissue-specific hormone/immune interface, reported a licensing agreement whereby Clarus will acquire the exclusive worldwide (excluding Australia) development and commercialization rights for HAVAH T+Ai (CLAR-121) (Press release, clarus therapeutics inc, MAY 25, 2021, View Source [SID1234580587]).

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CLAR-121 is a proprietary combination of testosterone (T) (natural ligand for the androgen receptor; AR) and anastrozole (inhibitor of T conversion to estradiol) delivered by a subcutaneous implant for treatment of AR-mediated breast disease that predominantly affects women. If approved, CLAR-121 would be the first T treatment of its kind for inflammatory breast disease, including inflammatory periductal mastitis (PDM) and estrogen receptor-positive (ER+) breast cancer. Clarus’s initial clinical development target is PDM — a destructive autoimmune inflammatory process of the retro-areolar milk ducts that results in multiple fistulae and inevitably results in disfiguring surgery and a high risk of recurrence. There is no known treatment for this condition apart from surgery, which has significant limitations.1 Due to the low prevalence of PDM in the U.S., Clarus anticipates this disease could qualify for orphan drug designation by the U.S. Food and Drug Administration and plans to petition the agency for that status for CLAR-121.

If approved, CLAR-121 would be the first T treatment of its kind for inflammatory breast disease.

HavaH has extensive clinical experience with CLAR-121 in more than 1,000 Australian women (more than 6,200 implants) with breast disease, and Clarus expects that access to HavaH’s pharmacokinetics, safety and early efficacy data in PDM will expedite progression to Phase 2/3 clinical studies in the U.S. Clarus estimates that the annual U.S. market size for PDM exceeds $400 million.2,3,4 With this new pipeline asset, Clarus may also pursue, alone or in partnership, future indications in ER+ breast cancer, macromastia, granulomatous mastitis, and autoimmune induced breast pain.

"This licensing agreement marks the beginning of an exciting new partnership with HavaH. Their experience coupled with the significant amount of clinical data generated in Australia will benefit Clarus greatly as we begin our development activities in the U.S.," said Dr. Robert Dudley, Clarus’s founder, president and CEO. "CLAR-121 allows us to leverage our expertise in androgen biology, as exemplified by JATENZO, a testosterone replacement therapy (TRT) for male hypogonadism and Clarus’s first commercial product, and expands our development pipeline with an initial focus on PDM in women — a debilitating, painful disease with very limited treatment options, short of invasive surgery. This treatment, if approved, has the potential to be life-changing for women who suffer from PDM, and its development fits well with our mantra: ‘good is never good enough’. Our goal is to provide treatment options that not only produce a positive clinical outcome, but also provide a positive therapeutic experience for patients."

Under the terms of the licensing agreement, Clarus will be responsible for future global development and regulatory activities for CLAR-121, excluding Australia. Clarus will pay HavaH an upfront payment of $500,000 upon signing and HavaH may be eligible for up to $10.75 million in potential development and regulatory milestone payments. HavaH will retain the right to promote HAVAH T+Ai in Australia. Additionally, HavaH would be eligible for a modest royalty and up to $30 million in potential commercial milestones.

"We developed HAVAH T+Ai to address a significant unmet need in women’s health, and our partnership with Clarus will enable us to advance this therapeutic approach not only for inflammatory breast disease but, more widely we hope, for ER+ breast cancer where data now unambiguously demonstrates that the androgen receptor has an important tumor suppressor role in this form of breast cancer,"5 said Stephen Birrell, MD, PhD, HavaH founder, chairman and chief medical officer.

"In Clarus, we found a partner who understands and appreciates the potentially profound importance of androgen action in the context of inflammatory breast disease, as well as its role as an adjunctive endocrine therapy for certain forms of breast cancer," said Kathy Harrison, HavaH CEO.

Reedland Capital Partners, acting through Weild & Co., member FINRA/SIPC, served as financial advisor to HavaH in connection with this transaction. For more information, please visit www.reedland.com.

Alloy Therapeutics and Pyxis Oncology Form Kyma Therapeutics to Develop Novel Immune-Modulating Antibodies for Cancer and Autoimmune Diseases

On May 25, 2021 Alloy Therapeutics ("Alloy") and Pyxis Oncology ("Pyxis") reported the formation of a joint venture named Kyma Therapeutics to develop immune-modulating antibodies for novel targets in cancer and autoimmune diseases (Press release, Pyxis Oncology, MAY 25, 2021, View Source [SID1234580586]). Kyma Therapeutics will advance programs directed to immune-modulating targets identified by Pyxis. Alloy Discovery Services will generate therapeutic candidates using Alloy’s broad suite of human antibody discovery technologies, including the ATX-Gx mouse platform while Pyxis will develop assays and perform ex-vivo and in-vivo studies on the therapeutic candidates.

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Under the terms of the agreement, Pyxis and Alloy intend to collaboratively fund and perform services for Kyma Therapeutics to rapidly develop programs to a value-inflection point with the objective that the programs will have the potential for independent financing and partnering. Pyxis and Alloy will retain certain rights to participate in the development and commercialization of products originating from Kyma Therapeutics.

"We are excited to partner with Pyxis on the formation of Kyma Therapeutics to advance novel biologics for cancer and autoimmune disease," said Errik Anderson, Chief Executive Officer and Founder of Alloy. "This joint venture combines Pyxis’ proprietary target discovery technology and expertise with Alloy’s high throughput antibody discovery engine, enabling the rapid development of high-impact immune-modulating therapeutics for underserved patient populations."

Lara Sullivan, M.D., Chief Executive Officer of Pyxis, added, "Kyma Therapeutics represents the successful execution of Pyxis’ and Alloy’s corporate strategies to bring new treatment options to patients with the highest capital efficiency. We look forward to working with Alloy to further advance these compelling treatments for patients with cancer and autoimmune diseases."

Chris Pacheco, Venture Partner at 82VS, Alloy’s affiliated venture studio, added, "Kyma Therapeutics embraces a new approach to streamline biotechnology company creation and the drug discovery process, alongside leading scientific entrepreneurs and target-rich companies. We are thrilled to advance this important pipeline in partnership with Pyxis, which will ultimately be for the benefit of patients."

The announcement follows in the footsteps of Broadwing Bio, a partnership between Alloy and Maze Therapeutics, which was formed in December 2020. Each year, 82VS is expected to launch five to ten new asset-centric companies such as Kyma and Broadwing, through partnerships with leading scientific entrepreneurs, large biopharma companies, and other target-rich venture-backed companies.

Nordic Nanovector Announces Update from Archer-1 Phase 1b Trial of Betalutin® in combination with rituximab in 2L Follicular Lymphoma

On May 25, 2021 Nordic Nanovector ASA (OSE: NANOV) reported that initial promising data from the Archer-1 Phase 1b trial investigating Betalutin (177Lu lilotomab satetraxetan) in combination with rituximab (RTX) in second-line follicular lymphoma (2L FL) (Press release, Nordic Nanovector, MAY 25, 2021, View Source [SID1234580585]).

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The preliminary results show clinical activity with seven out of seven patients achieving a response, including 5 complete responses and 2 partial responses. All responses are currently ongoing, 5 of them 2 years after Betalutin administration.

Across this patient group, Betalutin with RTX showed a very good safety profile, comparable to that of single agent Betalutin, with no dose limiting toxicities observed.

Archer-1 is a Phase 1b open-label, single-arm, multi-centre dose-escalation trial to assess the safety and preliminary activity of CD37-targeted Betalutin in combination with CD20-targeted RTX in patients with relapsed/refractory FL who have received one or more prior therapies.

The starting doses of Betalutin and lilotomab were 10MBq/kg and 40mg, respectively, which was escalated to Betalutin 15MBq/kg and lilotomab 40mg in the second cohort. Following Betalutin dosing, patients received four weekly doses of RTX (375mg/m2) on days 7, 14, 21 and 28. Patients who did not progress (including CR, PR, SD) were scheduled to receive RTX maintenance for 2 years.

The primary objective of the study was to evaluate the safety and tolerability of Betalutin in combination with RTX, the secondary objective to evaluate the preliminary anti-tumour activity of combination treatment.

The rationale for Archer-1 was provided by earlier preclinical data showing Betalutin can up-regulate CD20 expression in different rituximab-sensitive NHL cell lines and act synergistically with rituximab in a rituximab-sensitive NHL animal model and, more recently, that Betalutin has the potential to counteract resistance to rituximab in non-Hodgkin’s lymphoma models.

Peter Braun, Nordic Nanovector CEO, commented: "We are encouraged by the results in this small Phase I study in second line FL patients. Both the overall safety of this combination and the preliminary signs of efficacy are promising. We look at this study as an additional building block in our overall strategy to develop Betalutin for difficult to treat hematological tumors. Our near-term focus remains very much on completing PARADIGME in 3L FL and delivering top line 3-month data by the end of 2021.