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

On October 5, 2023 Isofol Medical AB (publ) (Nasdaq Stockholm: ISOFOL) ("Isofol"), reported that the company has taken notice of the results from the investigator-initiated study Modelle 001 (Press release, Isofol Medical, OCT 5, 2023, View Source [SID1234635683]).

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As previously informed, Sahlgrenska University Hospital in collaboration with Norrland University Hospital has conducted an investigator-initiated academic study, Modelle 001. The study included 30 patients and was led by Dr. Helena Taflin at Sahlgrenska University Hospital in Gothenburg. The aim of the study was to examine in detail the effect of different folates (arfolitixorin/leucovorin) in combination with 5-FU on patients with colorectal cancer that has metastasized to the liver.

The research team presented the final study results at the Folate Receptor Society’s 8th International Symposium on Folate Biology and Therapeutics in New York on 4 October 2023. The abstract is published via Sahlgrenska University Hospital:

View Source

"This is an investigator-initiated academic study where the main purpose was to study the effect of different folates on the inhibition of the enzyme thymidylate synthase (TS) in the tumour, in this case liver metastases, where a new method that needs to be validated has been used. No clinical parameters in terms of efficacy have been evaluated as only one dose was given to the limited number of patients included in the study. We see the results as a possible complement to our previously conducted pharmacodynamic (PD) and pharmacokinetic (PK) study from 2015, where the same research group was involved, however, we need to quality review the material when a study report is available", says acting CEO Roger Tell.

On October 5, 2023 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported that the U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on the lacutamab IND leading to a pause in new patient enrollment to the Company’s ongoing lacutamab trials IPH4102-201 (Phase 2 TELLOMAK) and 102 (Phase 1b PTCL). The partial clinical hold follows one fatal case of hemophagocytic lymphohistiocytosis (HLH), a rare hematologic disorder. Patients already on study treatment who are deriving clinical benefit may continue treatment after being reconsented.

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TELLOMAK, Innate Pharma’s ongoing Phase 2 trial of lacutamab in cutaneous T-cell lymphoma (CTCL), completed enrollment in Q2 2023 (n=170 patients). Enrollment is also completed to the initial cohort (n=20 patients) of the Phase 1b PTCL trial and is awaiting a futility interim analysis to progress to the next stage. Innate Pharma is on track for final data from the Phase 2 TELLOMAK trial and preliminary data on PTCL in Q4 2023.

"Patient safety is of paramount importance to us, and we are currently undertaking efforts to address the FDA requests, which include incorporation of risk mitigation and management strategies for hemophagocytic lymphohistiocytosis in ongoing lacutamab studies." said Mondher Mahjoubi, Chief Executive Officer of Innate Pharma. "Additionally, with all patients recruited into the Phase 2 TELLOMAK study, we do not currently anticipate any delay for the TELLOMAK Phase 2 final data due shortly."

About Lacutamab

Lacutamab is a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody that is currently in clinical trials for treatment of cutaneous T-cell lymphoma (CTCL), an orphan disease, and peripheral T cell lymphoma (PTCL). Rare cutaneous lymphomas of T lymphocytes have a poor prognosis with few efficacious and safe therapeutic options at advanced stages.

KIR3DL2 is an inhibitory receptor of the KIR family, expressed by approximately 65% of patients across all CTCL subtypes and expressed by up 90% of patients with certain aggressive CTCL subtypes, in particular, Sézary syndrome. It is expressed by up to 50% of patients with mycosis fungoides and peripheral T-cell lymphoma (PTCL). It has a restricted expression on normal tissues.

Lacutamab is granted European Medicines Agency (EMA) PRIME designation and US Food and Drug Administration (FDA) granted Fast Track designation for the treatment of patients with relapsed or refractory Sézary syndrome who have received at least two prior systemic therapies. Lacutamab is granted orphan drug status in the European Union and in the United States for the treatment of CTCL.

About TELLOMAK:

TELLOMAK (NCT03902184) is a global, open-label, multi-cohort Phase 2 clinical trial recruiting patients with Sézary syndrome and mycosis fungoides (MF) in the United States and Europe. Specifically:

Cohort 1: lacutamab being evaluated as a single agent in approximately 60 patients with Sézary syndrome who have received at least two prior systemic therapies, including mogamulizumab. The Sézary syndrome cohort of the study could enable the registration of lacutamab in this indication.
Cohort 2: lacutamab being evaluated as a single agent in patients with MF that express KIR3DL2, as determined at baseline with a Simon 2-stage design.
Cohort 3: lacutamab being evaluated as a single agent in patients with MF that do not express KIR3DL2, as determined at baseline, with a Simon-2 stage design.
All comers: lacutamab being evaluated as a single agent in patients with both KIR3DL2 expressing and non-expressing MF to explore the correlation between the level of KIR3DL2 expression and treatment outcomes utilizing a formalin-fixed paraffin embedded (FFPE) assay under development as a companion diagnostic.
The trial is now fully enrolled. The primary endpoint of the trial is objective global response rate. Key secondary endpoints are progression-free survival, duration of response, overall survival, quality of life, pharmacokinetics and immunogenicity and adverse events.

About the Phase 1b in PTCL:

The Phase 1b clinical trial (NCT05321147) is investigating lacutamab monotherapy in KIR3DL2-expressing patients with relapsed/refractory PTCL who have received at least one prior systemic therapy (N=20, with futility interim ungating N=20 expansion). The trial is designed to evaluate safety, as well as characterize clinical outcomes, pharmacokinetics and immunogenicity of lacutamab alone in PTCL. Further expansion will be determined based on preliminary efficacy signals.

On October 5, 2023, Equillium, Inc. (the "Company") reported to have entered into an Open Market Sale AgreementSM (the "Sale Agreement") with Jefferies LLC ("Jefferies"), pursuant to which the Company may, from time to time, offer and sell shares of the Company’s common stock, par value $0.0001 per share (the "Shares"), through Jefferies, as the Company’s sales agent and/or principal (Filing, 8-K, Equillium, OCT 5, 2023, View Source [SID1234635680]).

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The Shares will be offered and sold pursuant to the Company’s Registration Statement on Form S-3 (File No. 333-269153) (the "Registration Statement"), which was originally filed with the Securities and Exchange Commission ("SEC") on January 6, 2023, the base prospectus contained within the Registration Statement, and a prospectus supplement that was filed with the SEC on October 5, 2023 in connection with the offer and sale of the Shares pursuant to the Sale Agreement. The Shares may only be offered and sold by means of a prospectus, including a prospectus supplement, forming part of the effective Registration Statement.

The Company is not obligated to make any sales under the Sale Agreement and may at any time suspend sale of the Shares under the Sale Agreement. Any sales of Shares will be made by methods deemed to be an "at the market offering" as defined in Rule 415 promulgated under the Securities Act of 1933, as amended (the "Securities Act"), including privately negotiated transactions with the consent of the Company, block transactions, sales made directly on the Nasdaq Capital Market or sales made into any other existing trading market for the Company’s common stock. The Company intends to use the net proceeds of the offering to fund the continued development of any product candidates in the Company’s pipeline, and for working capital, capital expenditures and general corporate purposes.

Jefferies will act as sales agent and/or principal and will use commercially reasonable efforts consistent with its normal trading and sales practices to place all of the Shares requested to be sold by the Company. The Company will pay Jefferies a commission rate of 3.0% of the gross proceeds from the sales of Shares sold pursuant to the Sale Agreement. In addition, the Company has agreed to pay certain expenses incurred by Jefferies in connection with the offering. The Company has also provided Jefferies with customary representations, warranties, covenants, and indemnification rights. Both parties have the right to terminate the Sale Agreement upon written notice to the other party as specified in the Sale Agreement.

The foregoing description of the Sale Agreement does not purport to be complete and is qualified in its entirety by reference to the full Sale Agreement, a copy of which is attached hereto as Exhibit 1.1 and is incorporated herein by reference.

The legal opinion of Cooley LLP relating to the Shares being offered pursuant to the Sale Agreement is filed as Exhibit 5.1 to this Current Report on Form 8-K.

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