On July 8, 2024 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for patients with RAS-addicted cancers, reported that it will host an investor webcast to provide an update on its RMC-6236 pancreatic ductal adenocarcinoma (PDAC) clinical development program (Press release, Revolution Medicines, JUL 8, 2024, View Source [SID1234644716]). Speakers will include members of Revolution Medicines’ management team, along with Brian M. Wolpin, M.D., M.P.H., professor of medicine at Harvard Medical School, and director of the Gastrointestinal Cancer Center and Robert T. & Judith B. Hale Chair in Pancreatic Cancer at Dana-Farber Cancer Institute.

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The webcast will take place at 8:00 a.m. Eastern Time on Monday, July 15, 2024. To access the live webcast, please visit the "Events & Presentations" page of Revolution Medicines’ website at View Source Additionally, a replay of the webcast will be available on the "Events & Presentations" page of the Revolution Medicines website for at least 14 days following the event.

On July 8, 2024 PharmaMar (MSE:PHM) reported to have received a notification from the European Commission (EC) informing the Company of its decision to revoke the refusal to grant Marketing Authorization for Aplidin in Multiple Myeloma (Press release, PharmaMar, JUL 8, 2024, View Source [SID1234644715]).

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According to the communication received, the EC has re-evaluated the criteria applied for the participation of experts in the administrative procedure for the Marketing Authorization of Aplidin, as well as the relevant EMA rules governing conflicts of interest, so that they can ensure the objective impartiality of these experts.

Therefore, the EC notes that one of the experts of the Scientific Advisory Group (SAG) involved in the development of a rival product, was allowed to participate in the Marketing Authorization procedure for Aplidin, in accordance with the EMA rules applicable at the time.

Consequently, in order to avoid any doubt as to the objective impartiality of the assessment of the application, the Commission has decided it is appropriate to revoke the decision to refuse Marketing Authorization for Aplidin.

It is also reported that the Commission has forwarded to the EMA the opinions of the Committee for Medicinal Products for Human Use (CHMP), to request the re-evaluation of the application from the time of the onset of the detected procedural irregularity.

The European Commission’s reversal of the decision, which is totally exceptional, is a de facto acknowledgement that PharmaMar did not have all the necessary guarantees in the evaluation process for Aplidin. Now that the registration dossier has been returned to the EMA, the Company will ensure that the procedure is conducted with absolute impartiality and on a level playing field.

History of the lawsuit, 7 years of litigation

PharmaMar filed a lawsuit in October 2018 before the General Court of the European Union against the EC, seeking the annulment of the Commission’s Implementing Decision, by which it denied Marketing Authorization for Aplidin as a treatment for patients with Multiple Myeloma.

The reason for the lawsuit related to the strict conflict-of-interest checks carried out by the experts appointed by the EMA and the correct analysis of the scientific evidence presented by PharmaMar.

In October 2020, the General Court of the European Union upheld PharmaMar’s claim in full, at the extreme end of the conflict of interest, annulling the European Commission’s decision to refuse Marketing Authorization for Aplidin for the treatment of patients with Multiple Myeloma, and ordered the Commission to pay the costs.

In 2021, Estonia and Germany appealed the decision to the EU Court of Justice, although the EC decided not to do it, which could be understood as implicitly accepting the ruling.

In 2023, the Court of Justice of the European Union annulled the judgment of the General Court and referred the case back to the General Court, to rule again on the first ground for annulment urged by PharmaMar in its initial application, and to rule, if it considered it necessary, on the other claims for annulment in its action. That is, to rule not only on the conflict of interest and the breach of the Principle of Objective Impartiality by the EMA, but also on the breach of the Principle of Good Administration, the breach of the Principle of Equal Treatment and incorrect analysis of the scientific evidence presented by PharmaMar, the breach of the obligation to state reasons and the breach of the rights of defense.

The Company has always maintained that, during the evaluation process of its drug, Aplidin for the treatment of Multiple Myeloma, there was a conflict of interest of several members based on numerous objective elements, including the cooperation of one of its members with a Swedish company, XNK Therapeutics AB, developing a rival drug, as well as its participation in the development of other competing drugs.

Ligand Pharmaceuticals Incorporated (Nasdaq: LGND) reported that it has entered into a definitive agreement to acquire APEIRON Biologics AG, which holds royalty rights to QARZIBA (dinutuximab beta) for the treatment of high-risk neuroblastoma, for $100 million in cash (Press release, Ligand, JUL 8, 2024, View Source [SID1234644714]). In addition, Ligand will pay APEIRON shareholders additional consideration based on future commercial and regulatory events, including up to $28 million if QARZIBA royalties exceed certain predetermined thresholds by either 2030 or 2034, respectively.

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APEIRON is a private biopharmaceutical company based in Vienna, Austria. The company co-developed QARZIBA for the treatment of high-risk neuroblastoma in patients aged 12 months and above. QARZIBA was approved by the European Medicines Agency in 2017 and is commercially available today in more than 35 countries. APEIRON receives an undisclosed royalty on net sales of QARZIBA outside of mainland China from Recordati S.p.A, a leading global pharmaceutical company with a presence in over 150 countries and sales of more than $2.2 billion,2 and on net sales of QARZIBA within mainland China from BeiGene, Ltd.

"The addition of QARZIBA to our commercial royalty portfolio further supports our growth strategy to invest in high-value medicines that deliver significant clinical value and generate predictable and long-term revenue streams for our investors," said Todd Davis, CEO of Ligand. "QARZIBA is the only immunotherapy for high-risk neuroblastoma marketed across Europe and in other parts of the world. We believe this drug will be a meaningful contributor to our royalty revenue which is now driven by a diversified portfolio of 12 key commercial-stage products."

Peter Llewellyn-Davies, CEO of APEIRON commented, "This transaction is an important milestone for our company and shareholders. We have spent more than 20 years translating academic research into therapeutic products for diseases with high unmet needs. Our team was honored to help bring QARZIBA to the young patients who need it. We appreciate that Ligand recognizes the long-term potential of this critical drug for a rare pediatric cancer."

Transaction Terms
Under the terms of the agreement, which has been unanimously approved by both the Board of Directors at Ligand and APEIRON’s Supervisory Board, Ligand will acquire all the outstanding shares of APEIRON for $100 million in cash at closing. Ligand will also pay APEIRON shareholders additional consideration based on future commercial and regulatory events, including up to $28 million if QARZIBA royalties exceed certain predetermined thresholds by either 2030 or 2034, respectively. The transaction is subject to a 30-day shareholder objection period and other customary closing conditions and is expected to close in July 2024.

Concurrently, Ligand is also entering into a stock purchase agreement whereby it has committed to investing up to $4 million in invIOs Holding AG, a privately held spin-off of APEIRON. The proceeds will help finance the research and development of three innovative early-stage immuno-oncology assets. APEIRON is entitled to royalties and milestone payments on these assets which will further expand Ligand’s development stage portfolio. This transaction is expected to close in July 2024.

Financial Guidance Update
The APEIRON acquisition will be immediately accretive to Ligand’s earnings per share (EPS) by approximately $1.00 on an annualized basis. Ligand is increasing its 2024 revenue guidance to be in the range of $140 million to $157 million (previously $130 million to $142 million) and is raising core adjusted EPS guidance to $5.00 to $5.50 (previously $4.25 to $4.75). Royalties are now expected to range from $100 million to $105 million (previously $90 million to $95 million). Guidance for sales of Captisol is unchanged at $25 million to $27 million and contract revenue is now expected to range from $15 million to $25 million (previously $15 million to $20 million).

McDermott Will & Emery and E+H Rechtsanwälte GmbH served as Ligand’s legal counsel. Baker McKenzie and DORDA served as APEIRON’s legal counsel.

About QARZIBA
QARZIBA is a monoclonal antibody that is specifically directed against the carbohydrate moiety of disialoganglioside 2 (GD2), which is overexpressed on neuroblastoma cells. Dinutuximab beta was approved by the European Medicines Agency in 2017 for the treatment of high-risk neuroblastoma in patients aged 12 months and above, who have previously received induction chemotherapy and achieved at least a partial response, followed by myeloablative therapy and stem cell transplantation, as well as patients with history of relapsed or refractory neuroblastoma, with or without residual disease.

Dinutuximab beta was originally discovered by EMD Lexigen Research Center and ultimately developed by the Children’s Cancer Research Center (CCRI) and European Neuroblastoma Research Network (SIOPEN) for the treatment of high-risk neuroblastoma. APEIRON in-licensed dinutuximab beta from CCRI and SIOPEN in 2011, and upon completing the clinical development, out-licensed the exclusive global commercialization rights to EUSA Pharma (UK) Limited in 2016. QARZIBA is marketed outside of mainland China by the global pharmaceutical company Recordati S.p.A., which acquired EUSA Pharma (UK) Limited in 2022.

On July 8, 2024 Kineta, Inc. (Nasdaq: KA), a clinical-stage biotechnology company focused on the development of novel immunotherapies in oncology that address cancer immune resistance, reported that it has entered into an exclusivity and right of first offer agreement (the "Agreement") with TuHURA Biosciences, Inc. ("TuHURA"), a Phase 3 registration-stage immune-oncology company developing novel technologies to overcome resistance to cancer immunotherapy (Press release, Kineta, JUL 8, 2024, View Source;utm_medium=rss&utm_campaign=kineta-announces-exclusivity-and-right-of-first-offer-agreement-for-its-vista-blocking-antibody-with-tuhura-biosciences [SID1234644713]). Pursuant to the Agreement, among other things, Kineta has granted TuHURA an exclusive right to acquire Kineta’s worldwide patents, patent rights, patent applications, product and development program assets, technical and business information, and other rights and assets associated with and derived from its development program related to KVA12123, the Company’s VISTA blocking immunotherapy. This exclusive right shall continue through the first to occur of (a) the execution of any definitive agreement with respect to a potential transaction by TuHURA or one or more of its affiliates and (b) 11:59 PM Eastern Time on October 1, 2024, subject to extension. In consideration for Kineta’s compliance with its obligations set forth in the Agreement, TuHURA will pay Kineta a $5 million nonrefundable payment.

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KVA12123 is a novel VISTA blocking monoclonal antibody being evaluated in a Phase 1/Phase 2 clinical trial for patients with advanced solid tumors. The study includes a monotherapy arm with KVA12123 alone, and a combination arm utilizing KVA12123 together with Merck’s anti-PD1 therapy, KEYTRUDA (pembrolizumab). Initial results from this study were reported in April this year at the American Association of Cancer Research. To date, the drug has been well tolerated with no dose limiting toxicities and no cytokine release syndrome. Additional data is expected to be released in the fourth quarter of 2024.

"TuHURA Biosciences is well positioned to advance KVA12123," said Craig W. Philips, President of Kineta. "TuHURA is a Phase 3 registration stage immuno-oncology company with expertise and deep experience in the field. We believe they will make an excellent partner for this program and in advancing this novel drug program which could provide an important new treatment option for cancer patients."

Immix Biopharma, Inc. ("ImmixBio", "Company", "We" or "Us", "IMMX") (Nasdaq: IMMX), a clinical-stage biopharmaceutical company trailblazing cell therapies in AL Amyloidosis and autoimmune disease, reported that the 1st patient has been dosed at MSKCC in its U.S. NEXICART-2 trial with NXC-201, a sterically-optimized BCMA-targeted CAR-T cell therapy (Press release, Immix Biopharma, JUL 8, 2024, View Source [SID1234644712]).

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The NEXICART-2 study is intended to evaluate the safety and efficacy of NXC-201 in relapsed/refractory AL Amyloidosis patients with adequate cardiac function who have not been exposed to prior BCMA-targeted therapy. The study builds on positive data from the initial ex-U.S. study, NEXICART-1, presented at the 27th Annual Meeting of The American Society of Gene and Cell Therapy (ASGCT 2024) which showed a 92% overall response rate in relapsed/refractory AL Amyloidosis patients (12/13). The best responder experienced a 28.0 month duration of response (as reported May 10, 2024, with ongoing follow-up).

"I am excited to initiate the only CAR-T clinical trial currently recruiting for AL Amyloidosis patients that have progressed on front-line daratumumab (DARZALEX)-combination therapy," said Heather Landau, MD, Memorial Sloan Kettering Cancer Center Amyloidosis Program Director and NEXICART-2 principal study investigator. "A one-time therapy such as NXC-201 would provide an attractive option for AL Amyloidosis patients and clinicians. There are no approved drugs for relapsed/refractory AL Amyloidosis today."

"We believe initiation of the U.S. NEXICART-2 study is an important advancement in AL Amyloidosis. NXC-201 has the potential to become a first-in-class safe and durably-effective therapy for patients with relapsed/refractory AL Amyloidosis. We are humbled by the enthusiasm across the U.S. AL Amyloidosis community and look forward to robust enrollment for NEXICART-2," said Ilya Rachman, M.D., Ph.D., Chief Executive Officer of Immix Biopharma. Gabriel Morris, Chief Financial Officer of Immix Biopharma, added, "Dosing of the first patient in line with our mid-2024 guidance is a testament to the stellar execution of our extraordinary team and partners."

NXC-201 is the only CAR-T therapy currently in development in AL Amyloidosis, mentioned in a review article entitled "Systemic Light Chain Amyloidosis" published in June, 2024 New England Journal of Medicine.

About NEXICART-2
NEXICART-2 (NCT06097832) is an open-label, single-arm, multi-site U.S. Phase 1b/2 dose expansion clinical trial of CAR-T NXC-201 in relapsed/refractory AL Amyloidosis. NEXICART-2 is expected to enroll 40 patients with adequate cardiac function who have not been exposed to prior BCMA-targeted therapy. The study is designed with a standard 6 patient safety-run in to evaluate two doses (three patients each at 150 million CAR+T cells and 450 million CAR+T cells), with the potential for further escalation to 800 million CAR+T cells (all 3 dose levels were evaluated in the NEXICART-1 study and have produced complete responses in relapsed/refractory AL Amyloidosis patients). The study aims to evaluate the safety and efficacy of NXC-201 in this patient population. Primary endpoints are complete response rate and overall response rate, according to consensus recommendations (Palladini et al. 2012).

About NEXICART-1
NEXICART-1 (NCT04720313) is an open-label, ex-U.S. Phase 1b/2a clinical trial of NXC-201 (formerly HBI0101) in patients with relapsed/refractory multiple myeloma and relapsed/refractory AL amyloidosis (including AL Amyloidosis patients with impaired cardiac function and including AL Amyloidosis patients exposed to prior BCMA-targeted therapy). The primary objective of the study is to characterize the safety and efficacy, as well as confirm the recommended Phase 2 dose (RP2D) of NXC-201 (which has already been confirmed). NEXICART-1 clinical results, most recently from ASGCT (Free ASGCT Whitepaper) 2024, are available at View Source

About NXC-201
NXC-201 is a sterically-optimized BCMA-targeted chimeric antigen receptor T (CAR-T) cell therapy. Initial data from Phase 1b/2a ex-U.S. study NEXICART-1 has demonstrated short duration of cytokine release syndrome (CRS) and no grade 3 or delayed neurotoxicity in high-volume disease, as well as short duration CRS and no neurotoxicity of any kind in AL Amyloidosis.

NXC-201 is being studied in a comprehensive clinical development program for the treatment of patients with relapsed/refractory AL amyloidosis, with the potential to expand into autoimmune indications. The NXC-201 NEXICART-2 U.S. clinical trial builds on a robust clinical dataset. NXC-201 has been awarded Orphan Drug Designation (ODD) in the US by the FDA and in the EU by the EMA in AL Amyloidosis.

About AL Amyloidosis
AL amyloidosis is caused by abnormal plasma cells in the bone marrow, which produce misfolded amyloid proteins that build-up in the heart, kidney, liver, and other organs. This build-up causes progressive and widespread damage to multiple organs, including heart failure, and leads to high mortality rates.

The U.S. observed prevalence of relapsed/refractory AL Amyloidosis is estimated to be growing at 12% per year according to Staron, et al Blood Cancer Journal, to approximately 33,277 patients in 2024.

The Amyloidosis market was $3.6 billion in 2017, and is expected to reach $6 billion in 2025, according to Grand View Research.