On October 5, 2023 Vedanta Biosciences, a clinical-stage biopharmaceutical company pioneering the development of oral therapies based on defined bacterial consortia, reported that members of its executive team will participate at the following investor conferences (Press release, Vedanta Biosciences, OCT 5, 2023, View Source [SID1234635689]):

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BMO Life Sciences Private Company Showcase

Presentation Date: October 12, 2023

Presentation Time: 2:55 p.m. ET

Location: The New Your Times Building, New York, NY

Leerink Partners Biopharma Private Company Connect

Dates: October 25-26, 2023

Virtual 1×1 meetings only

On October 5, 2023 Perspective Therapeutics, Inc. ("Perspective" or "the Company") (NYSE AMERICAN: CATX), a precision oncology company developing alpha-particle therapies and complementary diagnostic imaging agents and an innovator in seed brachytherapy treatment options for multiple cancers, reported that long-term data regarding Cesium-131 brachytherapy in the treatment of prostate cancer, as well as preliminary long-term data of Cesium-131 utilized in salvage treatment of recurrent cervical and uterine cancers were presented at the American Society for Radiation Oncology’s (ASTRO) Annual Conference held in San Diego, from October 1-4, 2023 (Press release, Perspective Therapeutics, OCT 5, 2023, View Source [SID1234635687]).

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The first presentation, entitled "Long-Term Urinary Toxicity Follow-Up of Combined External Beam Radiation and Cs-131 LDR Brachytherapy Boost for Prostate Cancer," was presented by Mohamed Abdelhakiem, MD from the UPMC Hillman Cancer Center in Pittsburgh, PA. The presentation described urinary data collected from 341 patients treated with Cesium-131 between 2006 and 2022.

The second presentation, entitled "Cesium-131 Low-Dose Rate Interstitial Brachytherapy as a Salvage Re-Irradiation Technique in Treating Cervical and Uterine Cancer Pelvic Recurrence with Prior History of Pelvic Radiation," was presented by Zeta Chow, MD, MS from the University of Kentucky in Lexington, KY. The aim of the study was to report local cancer control rates and the toxicity profile of Cesium 131 brachytherapy as a salvage re-irradiation option for patients with recurrent disease. The authors concluded that Cesium-131 brachytherapy is a promising alternative to pelvic exenteration, which can be a significant surgical procedure.

"We’re excited that UPMC’s long term data on Cesium-131 brachytherapy for prostate cancer was included at this year’s ASTRO meeting," said Thijs Spoor, Perspective’s Chief Executive Officer. "ASTRO’s inclusion of the University of Kentucky’s promising data describing Cesium-131 brachytherapy in a challenging group of gynecological patients reinforces its value as the isotope of choice for brachytherapy treatment in multiple tumors."

Perspective Therapeutics is the world’s only producer of Cesium-131 seeds for brachytherapy which provide expanding internal radiation treatment options throughout the body for prostate cancer as well as difficult to treat lung, brain, gynecological, head and neck, pelvic, and colorectal cancers.

Additional details about these presentations can be found on the ASTRO website (www.astro.org).

On October 5, 2023 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported that the first patient has been dosed in the Phase 1/2 dose escalation/dose expansion study of ONCT-534, the company’s dual-action androgen receptor inhibitor (Press release, Oncternal Therapeutics, OCT 5, 2023, View Source [SID1234635686]).

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"The dosing of the first patient with ONCT-534 is an important milestone for patients suffering from advanced prostate cancer who have relapsed or are refractory after treatment with AR signaling inhibitors," said Salim Yazji, M.D., Oncternal’s Chief Medical Officer. "Preclinical studies suggest that ONCT-534 may address important tumor escape mechanisms that result in resistance to currently available AR inhibitors, such as enzalutamide or abiraterone. We intend to advance the dose escalation portion of the Phase 1/2 Study ONCT-534-101 quickly, and we will be enrolling patients in sites across the U.S. over the coming weeks, and in the United Kingdom in early 2024. We expect to report initial clinical data in the first half of 2024."

ONCT-534 is a dual-action androgen receptor inhibitor (DAARI) that interacts with both the N-terminal domain and the ligand-binding domain (LBD) of the androgen receptor (AR), inhibiting cell growth and inducing AR degradation. Preclinical studies have shown activity in prostate cancer models against both unmutated AR, and against multiple mutations, including AR amplification, mutations in the AR LBD, and splice variants with loss of the AR LBD.

About Study ONCT-534-101
Study ONCT-534-101 is a Phase 1/2, single-arm, open-label, multi-center study to evaluate the safety and tolerability, pharmacokinetics, and anti-tumor activity of ONCT-534 in patients with metastatic castration-resistant prostate cancer (mCRPC) who have relapsed or are refractory to approved androgen receptor signaling inhibitors (ARSIs) including enzalutamide, abiraterone, apalutamide and darolutamide. After the safety and tolerability of ONCT-534 have been assessed to select the recommended Phase 2 dose (RP2D) in Phase 1, Phase 2 will commence to further validate the dose and evaluate the safety and efficacy of ONCT-534.

On October 5, 2023 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the Phase 3 AMBASSADOR (A031501) trial (KEYNOTE-123) evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, met one of its dual primary endpoints of disease-free survival (DFS) for the adjuvant treatment of patients with localized muscle-invasive urothelial carcinoma (MIUC) and locally advanced urothelial carcinoma versus observation (Press release, Merck & Co, OCT 5, 2023, View Source [SID1234635685]). At a pre-specified interim analysis review conducted by an independent Data Monitoring Committee, KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in DFS versus observation in these patients after surgery. The trial will continue to evaluate its other dual primary endpoint of overall survival (OS). The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies; no new safety signals were identified. Results will be presented at an upcoming medical meeting and discussed with regulatory authorities.

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"Up to half of patients with bladder cancer who undergo surgery will experience recurrence within a year, underscoring the need for new treatment options in the adjuvant setting," said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. "These positive results highlight the potential of KEYTRUDA to prevent recurrence after surgery for patients with localized muscle-invasive or locally advanced urothelial carcinoma."

This trial was sponsored by the U.S. National Cancer Institute (NCI), part of the National Institutes of Health. Alliance for Clinical Trials in Oncology designed and led the trial with funding from the NCI and participation from all the National Clinical Trials Network Groups. Merck provided funding and support through a Cooperative Research and Development Agreement between Merck and NCI.

Merck has an extensive clinical development program evaluating KEYTRUDA as monotherapy and in combination with other anti-cancer therapies across all stages of bladder cancer, including non-muscle-invasive, muscle-invasive and metastatic. Phase 3 studies in muscle-invasive bladder cancer include the KEYNOTE-866 trial, as well as the Phase 3 KEYNOTE-B15 and Phase 3 KEYNOTE-905 trials, which are being conducted in collaboration with Seagen and Astellas.

About A031501 AMBASSADOR/KEYNOTE-123

AMBASSADOR (A031501, KEYNOTE-123) is a randomized, open-label Phase 3 trial (ClinicalTrials.gov, NCT03244384) evaluating KEYTRUDA versus observation for the adjuvant treatment of patients with localized MIUC and locally advanced urothelial carcinoma. The dual primary endpoints are OS and DFS, and secondary endpoints include OS and DFS in PD-L1 positive and negative patients. The trial enrolled 702 patients who were randomized to receive KEYTRUDA (200 mg intravenously every three weeks for up to 18 cycles) or undergo observation.

About bladder cancer

It is estimated that approximately 82,290 people in the U.S. will be diagnosed with bladder cancer in 2023, and approximately 7% of bladder cancer cases are locally advanced at diagnosis. Globally, there were approximately 573,000 new cases. Muscle-invasive bladder cancer is bladder cancer that has spread into the deep muscle of the bladder wall, and locally advanced urothelial cancer is cancer that begins in the urothelial cells and has spread from where it started to nearby tissue or lymph nodes. Despite surgery, up to 50% of patients with bladder cancer experience recurrence within 12 months.

On October 5, 2023 Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151) a Japan-based global specialty pharmaceutical company (J-GSP) creating innovative medical solutions utilizing the latest biotechnology, and Orchard Therapeutics plc (Orchard Therapeutics, Nasdaq: ORTX), a global gene therapy leader, reported the companies have entered into a definitive agreement under which Kyowa Kirin will acquire Orchard Therapeutics for $16.00 per American Depositary Share (ADS) in cash (approximately $387.4 million, or ¥57.3 billion), under which Orchard shareholders will hold an additional contingent value right (CVR) of $1.00 per ADS (Press release, Kyowa Hakko Kirin, OCT 5, 2023, View Source [SID1234635684]). An additional $1.00 CVR will be paid for a total of $17.00 per ADS, or approximately $477.6 million (¥70.7 billion) if the conditions are met.

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Kyowa Kirin has established a 2030 Vision to consistently create and deliver medicines with life-changing value that ultimately makes people smile, as a J-GSP. At the core of this strategy is a commitment to life, and a desire to match transformative science to areas of great unmet need.

Kyowa Kirin believes the potential of cell and gene therapies to help patients aligns well with its Vision, patient commitment, and emerging expertise in commercializing rare disease medicines worldwide. The gene therapy approach pioneered by Orchard Therapeutics harnesses the unique power of a patient’s own genetically modified hematopoietic stem cells (HSCs) to potentially correct the underlying cause of a genetic disease using a single administration.

Upon closing, the acquisition would provide Kyowa Kirin with a global leadership position in the burgeoning field of genetic medicine, including a portfolio spanning commercial, clinical, and pre-clinical HSC gene therapies designed to address serious diseases where the burden is immense for patients, families and society and current treatment options are limited or do not exist.

Orchard Therapeutics’ portfolio comprises Libmeldy (atidarsagene autotemcel), also known as OTL-200, intended for eligible patients with early-onset metachromatic leukodystrophy (MLD), a rare and life-threatening inherited disease of the body’s metabolic system. In the most severe form of MLD, babies develop normally but in late infancy start to rapidly lose the ability to walk, talk and interact with the world around them. Libmeldy is approved by the European Commission (EC) and UK Medicines and Healthcare products Regulatory Agency (MHRA) for the treatment of "late infantile" and "early juvenile" MLD patients. It is currently an investigational drug under Priority Review by the Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) goal date of March 18, 2024.

Using the same HSC gene therapy technology platform, Orchard Therapeutics is progressing two clinical-stage programs known as OTL-203 and OTL-201 for the treatment of another group of severe pediatric neurometabolic disorders, mucopolysaccharidosis type I Hurler’s syndrome (MPS-IH) and mucopolysaccharidosis type IIIA (MPS-IIIA), also known as Sanfilippo syndrome, respectively.

This acquisition will allow Kyowa Kirin to maximize the value of Libmeldy and efficiently accelerate the development of Orchard Therapeutics’ next-in-line MPS programs, as well as its other early research programs, including a severe, genetic form of Crohn’s disease and frontotemporal dementia (FTD). Furthermore, the combination of Orchard Therapeutics’ innovative HSC gene therapy platform technology and Kyowa Kirin’s capabilities, resources and infrastructure will enable the continued development of numerous promising biopharmaceutical candidates with the potential to deliver life-changing value in medical care, including in therapeutic areas and indications where Kyowa Kirin has deep experience, such as oncology and autoimmune diseases.

"We are excited to announce that we have signed the Transaction Agreement to acquire Orchard Therapeutics, one of the leading providers of HSC gene therapy." said Takeyoshi Yamashita, Ph.D., Director of the Board, chief medical officer, senior managing executive officer of Kyowa Kirin. "With this transaction, we anticipate being able to use a new modality that can have a profound impact on patients’ lives. Orchard Therapeutics is a company with a steady track record in this field and has already launched its HSC gene therapy in Europe and filed for review in the U.S. Our hope is to combine the strengths of Kyowa Kirin and Orchard Therapeutics with mutual respect to realize the successful creation and delivery of life-changing value for patients living with rare and life-threatening inherited diseases."

"This is an exciting opportunity designed to accelerate the realization of our shared vision of ending the devastation caused by severe genetic diseases and deliver life-changing value in medical care," said Bobby Gaspar, co-founder and chief executive officer of Orchard Therapeutics. "We remain as true to our mission as ever, and joining Kyowa Kirin’s global network ensures we are well-resourced to progress anticipated commercialization of OTL-200 in the U.S., if approved, continue investing in initiatives aimed at accelerating Libmeldy growth in Europe, capitalize on opportunities for global expansion, as well as advance our next-in-line neurometabolic programs in MPS disorders and earlier-stage research programs.

We look forward to collaborating with our new colleagues at Kyowa Kirin to fully unlock the curative potential of HSC gene therapy for the benefit of patients and society." Kyowa Kirin will hold a conference for investors on October 5 at 18:30 p.m. JST. Outline of the transaction Under the terms of the agreement, Kyowa Kirin will initiate a scheme of arrangement to acquire all Orchard Therapeutics’ ADSs at a price of $16.00 per ADS in cash (or aggregated value of approximately $387.4 million, or approximately ¥57.3 billion) at closing, which represents a premium of 144% to Orchard Therapeutics’ volume-weighted average price per ADS over the previous 30 days ended October 4. In connection with the transaction, a non-transferable CVR will be distributed to Orchard Therapeutics shareholders.

Holders of the CVR will be entitled to receive a cash payment of $1.00 per ADS related to the approval of OTL-200 for the treatment of MLD in the U.S. as defined in the CVR Agreement. Warrants outstanding as of the date of the Transaction Agreement will continue to be satisfied in accordance with their terms. The transaction has been unanimously approved by both company’s Board of Directors and is expected to close in the first quarter of 2024 subject to Orchard Therapeutics’ shareholder approval, receipt of applicable regulatory approvals and other customary closing conditions. Following the completion of the acquisition, Orchard Therapeutics will become a whollyowned subsidiary of Kyowa Kirin.

Kyowa Kirin is represented by Goldman Sachs Japan Co., Ltd. as financial advisor and Morrison & Foerster LLP. as legal advisor. Orchard Therapeutics is represented by Guggenheim Securities, LLC as financial advisor, Goodwin Procter LLP as U.S. legal advisor, and Slaughter & May Ltd. as UK legal advisor