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.

On July 8, 2024, IDEAYA Biosciences, Inc. (the "Company") reported clinical data from the Company’s ongoing Phase 2 monotherapy expansion dose of IDE397 in patients with methylthioadenosine phosphorylase (MTAP)-deletion urothelial cancer and non-small cell lung cancer ("NSCLC") (Press release, Ideaya Biosciences, JUL 8, 2024, View Source [SID1234644711]). IDE397 is the Company’s potent and selective potential first-in-class methionine adenosyltransferase 2 alpha (MAT2A) inhibitor in Phase 2 clinical trials for the treatment of MTAP-deletion solid tumors.

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The interim Phase 2 monotherapy expansion data for IDE397 in MTAP-deletion urothelial cancer and NSCLC demonstrated preliminary clinical efficacy and a favorable safety profile. The reported Phase 2 clinical data are based on 18 evaluable patients enrolled in the IDE397 Phase 2 monotherapy study at the expansion dose of 30 mg once-a-day ("QD") of IDE397. The heavily pre-treated MTAP-deletion urothelial cancer and NSCLC patients, including seven urothelial cancer patients, four adenocarcinoma NSCLC patients and seven squamous NSCLC patients, had a median of two prior lines of therapy, ranging from one to seven prior lines of treatment. Reported clinical efficacy and tolerability data are preliminary and based on investigator review from an unlocked database as of the data analysis cutoff date of June 21, 2024.

The Company reported an overall response rate of approximately 39% (one complete response and six partial responses by RECIST 1.1 evaluation), which includes two unconfirmed partial responses (one urothelial cancer patient that had a 100% tumor reduction in the target lesion at the last CT-scan assessment and one adenocarcinoma NSCLC patient). The complete response and two of the partial responses observed were in urothelial cancer patients, and among the evaluable patients with lung cancer, three of the partial responses observed were in squamous NSCLC patients and one of the partial responses observed was in an adenocarcinoma NSCLC patient.

The Company also observed a disease control rate of 94%, including one complete response, six partial responses and ten stable disease by RECIST 1.1 evaluation. In addition, the Company observed tumor shrinkage in 14 of the 18 evaluable patients. Of the evaluable patients, 11 are still on treatment and five of the seven responses by RECIST 1.1 evaluation remain in response. The median duration of treatment, median duration of response and median progression free survival have not yet been reached.

The Company also reported a ctDNA molecular response ("MR") rate of 81%, representing 13 of 16 reportable patients with 50% or greater ctDNA reduction (several quality control failures of patient samples precluded the other patients from MR analysis). In addition, the 30 mg QD expansion dose achieved target drug coverage and plasma S-adenosyl-l-methionine pharmacodynamic reduction associated with preclinical tumor regressions.

The interim Phase 2 monotherapy expansion data for IDE397 in MTAP-deletion urothelial cancer and NSCLC demonstrated a favorable adverse event ("AE") profile at the 30 mg QD expansion dose. Approximately 5.6% of patients experienced a Grade 3 or higher drug-related AE at the 30 mg QD dose, represented by one instance of Grade 3 asthenia, and no drug-related serious adverse events were observed. The Company observed no drug-related AEs leading to discontinuations, and one non-evaluable patient discontinued treatment due to rapid clinical progression of cancer fatigue and drug-unrelated adverse events in the first cycle of treatment. The Company anticipates that the favorable AE profile and dosing convenience of a 30 mg QD tablet has the potential to enable long-term dosing and combination development.

There are currently no FDA-approved therapies for patients with MTAP-deletion solid tumors, highlighting the unmet medical need. The priority MTAP-deletion solid tumor types for the IDE397 Phase 2 monotherapy program are urothelial cancer and NSCLC. MTAP-deletion prevalence has been reported at over 15% in NSCLC and over 25% in urothelial cancer, based on The Cancer Genome Atlas ("TCGA") database. The Company estimates that the MTAP-deletion annual incidence in the U.S. in NSCLC and urothelial cancer is approximately 48,000 patients, based on the 2024 Surveillance, Epidemiology, and End Results database. In addition, there are several potential expansion MTAP-deletion solid tumor types that are also being considered for monotherapy and combination development, including pancreatic, head and neck, gastric, and squamous esophageal cancer, among others. Based on the TCGA database, MTAP-deletion prevalence in pancreatic, head and neck, gastric, and squamous esophageal cancer represents an aggregate U.S. annual incidence of approximately 27,000 patients.

The Company has activated over 35 clinical trial sites globally in the U.S., Canada, Europe, and Asia Pacific to enable potential rapid enrollment for the IDE397 Phase 2 monotherapy expansion in MTAP-deletion lung and bladder cancer in its ongoing trial (NCT04794699). There is also an Amgen-sponsored Phase 1/2 trial of IDE397 and AMG 193 combination in MTAP-Deletion NSCLC (NCT05975073) for which the companies intend to develop a joint publication strategy in 2024. In addition, the Company has initiated enrollment in a Phase 1 clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of IDE397 in combination with Trodelvy (NCT04794699). The Company is also advancing multiple preclinical stage MTAP-deletion programs to enable wholly-owned combinations with IDE397, including a program targeting a development candidate nomination in the second half of 2024.

On July 8, 2024 Defence Therapeutics Inc. ("Defence" or the "Company"), (CSE: DTC, OTCQB: DTCFF, FSE: DTC), a Canadian biopharmaceutical company developing novel immune-oncology vaccines and drug delivery technologies, reported that it received a No Objection Letter ("NOL") from Health Canada for its Clinical Trial Study number ACCUM-002-01 entitles "A Phase I trial of Intratumoral Administration of ACCUM-002TM as a Monotherapy and in Combination with Opdualag in Patients with Unresectables, Stage IIIB and IV, Melanoma" (Press release, Defence Therapeutics, JUL 8, 2024, View Source;utm_medium=rss&utm_campaign=defence-receives-no-objection-letter-from-health-canada-for-phase-i-trial-of-its-accum-002-accutox-as-an-anti-cancer-molecule-in-patients-with-melanoma [SID1234644710]).

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The primary objectives of this study are to determine the safety and tolerability of intratumoral administration of AccuTOX, as a monotherapy and in combination with Opdualag which combines the LAG-3 checkpoint inhibitor relatlimab and PD-1 inhibitor nivolumab. The secondary objectives are to obtain preliminary efficacy data and to determine the Maximum Tolerated Dose ("MTD") and recommended Phase 2 Dose ("RP2D") of AccuTOX exploits as immune booster and anti-cancer molecule.

According to Vision Research Reports, the global cancer immunotherapy market size was estimated at USD 125.73 billion in 2023 and it is projected to increase USD 280.11 billion by 2033 with a CAGR of 8.34% from 2024 to 2033.

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The Defence’s team is already preparing this Phase I in Canada, most likely to be conducted in both Quebec and Ontario from which the hospitals sites will be confirmed upon agreements finalization.

"AccuTOX is Defence’s flagship asset in the anti-cancer therapeutics field and this Phase I clinical trial shall demonstrate and confirm primarily its safety and secondly its potency. We are thrilled to getting ready for this Phase I in Canada. Defence remains committed to its mission of addressing unmet clinical needs and in pursuing its goals to become a global leader in the development of innovative anti-cancer therapies," said Sebastien Plouffe, Chief Executive Officer of Defence Therapeutics.