Regeneron Announces Formation of Regeneron Cell Medicines with the Acquisition of 2seventy bio Platforms and Preclinical and Clinical Programs

On January 30, 2024 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported the formation of Regeneron Cell Medicines based on an agreement with 2seventy bio, Inc. to acquire full development and commercialization rights to its pipeline of investigational novel immune cell therapies, along with its discovery and clinical manufacturing capabilities (Press release, Regeneron, JAN 30, 2024, View Source [SID1234639713]). 2seventy bio employees who support the acquired programs will join Regeneron Cell Medicines, a newly formed research & development (R&D) unit to advance cell therapies and combination approaches in oncology and immunology.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Regeneron and 2seventy share a relentless commitment to push the boundaries of science in pursuit of therapies that can improve people’s lives. Our expertise in antibody technologies and emerging genetics capabilities, combined with 2seventy’s cell therapy platforms, presents a significant opportunity to address cancer and other serious diseases in new and impactful ways," said George D. Yancopoulos, M.D., Ph.D., Board Co-Chair, Co-Founder, President and Chief Scientific Officer of Regeneron. "By integrating 2seventy’s pipeline of cell therapies and their talented team, we are complementing our own expertise and portfolio of innovative immuno-oncology treatments, which will allow for potentially transformative combinations that can really make a difference in patients’ lives."

In 2018, Regeneron and bluebird bio (which subsequently spun out 2seventy bio in 2021) entered into an agreement to leverage their complementary technologies to discover novel cell therapy approaches to address cancer. Under the original agreement, Regeneron had the right to opt-in to a co-development/co-commercialization arrangement for collaboration targets. Under the terms of the new agreement, Regeneron will acquire full development and commercialization rights of 2seventy bio’s preclinical and clinical stage pipeline and will assume ongoing program, infrastructure and personnel costs related to these programs. There will be an upfront payment of $5 million and a single milestone payment from Regeneron to 2seventy bio for the first major market approval of the first approved product. Regeneron will pay 2seventy bio a low single-digit percent royalty on revenues generated by the products. The transaction is expected to close in the first half of 2024 subject to certain closing conditions including SEC-filings required by 2seventy bio and landlord consent of the sublease agreements.

To realize the full potential of these programs and capabilities, Regeneron Cell Medicines has been created to advance the next generation of cell therapies and explore combinations with Regeneron’s proprietary antibodies and bispecifics. An estimated 150 employees from 2seventy bio will transition to Regeneron to continue their work on cell therapy programs and will remain located in Cambridge, MA and Seattle, WA. Philip Gregory, D.Phil., currently the Chief Scientific Officer of 2seventy bio, will be appointed Senior Vice President and Head of Regeneron Cell Medicines upon closing of the transaction.

"Being part of Regeneron not only supercharges our ability to execute on our current portfolio of CAR T and T cell receptor programs but also creates unique opportunities for the combination of cell-based medicines with antibodies and other Regeneron biologics. Moreover, we can immediately build upon the strength of our longstanding relationship and our shared innovation-focused and science-driven approach to create new medicines for patients in need," said Philip Gregory, D.Phil., who, as noted above, will be appointed Senior Vice President, Head of Regeneron Cell Medicines. "We are excited to join an organization with decades of proven scientific innovation and the resources and visionary mindset to make Regeneron Cell Medicines a success."

Developing precision medicine for the treatment of cancer

On January 30, 2024 Kura Oncology presented tis corporate presentation (Presentation, Kura Oncology, JAN 30, 2024, View Source [SID1234639711]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!


Kura Oncology Reports Positive Preliminary Ziftomenib Combination Data in Acute Myeloid Leukemia

On January 30, 2024 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported preliminary clinical data from the first 20 patients in KOMET-007, a Phase 1 dose-escalation trial of the Company’s potent and selective menin inhibitor, ziftomenib, in combination with standards of care, including cytarabine/daunorubicin (7+3) and venetoclax/azacitidine (ven/aza), in patients with NPM1-mutant (NPM1-m) and KMT2A-rearranged (KMT2A-r) acute myeloid leukemia (AML) (Press release, Kura Oncology, JAN 30, 2024, View Source [SID1234639710]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The first 20 patients were enrolled in KOMET-007 between July 2023 and November 2023, including five newly diagnosed patients with adverse risk1 NPM1-m or KMT2A-r AML and 15 patients with refractory/relapsed (R/R) NPM1-m or KMT2A-r AML.

Continuous daily dosing of ziftomenib at 200 mg QD has been well tolerated and the safety profile consistent with features of underlying disease and backbone therapies. No differentiation syndrome events of any grade were reported, and no dose-limiting toxicities, evidence of QTc prolongation, drug-drug interactions or additive myelosuppression were observed.

As of the data cutoff on January 11, 2024, all newly diagnosed patients treated with ziftomenib and 7+3 achieved a complete remission (CR) with full count recovery, for a CR rate of 100% (5/5), including four patients with NPM1-m AML and one patient with KMT2A-r AML.

The overall response rate (ORR) among R/R patients treated with ziftomenib and ven/aza was 53% (8/15). Among all patients treated with ziftomenib and ven/aza, 40% (6/15) received prior treatment with a menin inhibitor. The CR/CRh2 rate in patients who were menin inhibitor naïve was 56% (5/9), including 60% (3/5) in patients with NPM1-m AML and 50% (2/4) in patients with KMT2A-r AML. The ORR in patients who received prior venetoclax was 40% (4/10), including 60% (3/5) in patients with NPM1-m AML.

As of the data cutoff, 80% (16/20) of patients remain on trial, including 100% (11/11) of all NPM1-m patients.

"Ziftomenib is one of the most exciting investigational agents being studied in AML, and I am thrilled to see the rapid pace of accrual into this first-in-human combinational study," said Amer Zeidan, MBBS, MHS, interim chief of the Division of Hematologic Malignancies, Director of Hematology Early Therapeutics Research at Yale Cancer Center and lead investigator of the KOMET-007 trial. "In this first public release of early data from the KOMET-007 trial, ziftomenib demonstrates an encouraging safety and tolerability profile in combination with 7+3 and ven/aza, enabling continuous administration while mitigating the risk of differentiation syndrome. The combinations demonstrate encouraging preliminary evidence of clinical activity in patients with refractory/relapsed disease after failure of other agents, including venetoclax, a setting with very limited effective treatment options. Further, the fact that most patients remain on study as of the data cutoff is notable in such difficult-to-treat patient populations."

The 200 mg dose of ziftomenib has been cleared in the R/R ven/aza cohorts and enrollment at the 400 mg dose is ongoing. Upon determination of a recommended Phase 2 dose, Kura plans to initiate a Phase 1b dose validation/expansion in combination with ven/aza in newly diagnosed patients with NPM1-m (without adverse risk) or KMT2A-r AML.

"We are highly encouraged by these preliminary combination data for ziftomenib and believe they support advancement into the frontline AML population," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "Given that ziftomenib targets foundational mutations at the core of up to 50% of AML cases, we are encouraged by its potential to transform treatment outcomes across the continuum of care. We continue to see strong investigator enthusiasm as evidenced by rapid enrollment across studies, and we expect to complete enrollment of all 85 patients in KOMET-001, our Phase 2 registration-directed trial of ziftomenib in patients with R/R NPM1-m AML, by the middle of this year. With the recently announced financing, we remain in a strong financial position with cash runway expected into 2027, which enables us to invest aggressively in research, development and pre-commercial activities to maximize value of ziftomenib and other pipeline assets."

Virtual Investor Event

Kura will host a virtual investor event featuring company management and investigators from the KOMET-007 trial of ziftomenib today at 8:00 a.m. ET. The live call may be accessed by dialing (800) 715-9871 for domestic callers and (646) 307-1963 for international callers and entering the conference ID: 7854712. A live webcast will be available here and in the Investors section of Kura’s website, with an archived replay available shortly after the event.

About Acute Myeloid Leukemia

AML is the most common acute leukemia in adults and begins when the bone marrow makes abnormal myeloblasts (white blood cells), red blood cells or platelets. Despite the many available treatments for AML, prognosis for patients remains poor and a high unmet need remains. The menin pathway is considered a driver for multiple genetic alterations of the disease, of which NPM1-mutations are among the most common, representing approximately 30% of AML cases and KMT2A-rearrangements represent approximately 5-10% of AML cases. While patients with NPM1-m AML have high response rates to frontline therapy, relapse rates are high and survival outcomes are poor, with only 30% overall survival at 12 months in the R/R setting. Additionally, NPM1 mutations frequently occur with co-mutations in other disease-associated genes, including FLT3, DNMT3A and IDH1/2, with prognosis heavily influenced by the occurrence of co-occurring mutations. Adult patients with NPM1-m AML and select co-mutations and/or R/R disease have a poor prognosis, with median overall survival of only approximately 7.8 months in 2nd line, 5 months in 3rd line and 3.5 months following the 4th line3. Adult patients with KMT2A-r AML have a poor prognosis with high rates of resistance and relapse following standard of care, with median overall survival for this patient population of only 6 months following 2nd line and 2.4 months following 3rd line4. No FDA-approved therapies targeting NPM1-m and KMT2A-r AML currently exist.

About Ziftomenib

Ziftomenib is a novel, once-daily, oral investigational drug candidate targeting the menin-KMT2A/MLL protein-protein interaction for treatment of genetically defined AML patients with high unmet need. In preclinical models, ziftomenib inhibits the KMT2A/MLL protein complex and exhibits downstream effects on HOXA9/MEIS1 expression and potent anti-leukemic activity in genetically defined preclinical models of AML. Ziftomenib has received Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of AML. Additional information about clinical trials for ziftomenib can be found at kuraoncology.com/clinical-trials/#ziftomenib.

Invitae Partners with BridgeBio Pharma to Harness Genetic Insights for the Discovery of Rare Disease Therapeutics

On January 30, 2024 Invitae (NYSE: NVTA), a leading medical genetics company, reported a partnership with BridgeBio Pharma, Inc. (Nasdaq: BBIO), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, designed to advance genetics-based drug discovery for rare diseases (Press release, Invitae, JAN 30, 2024, View Source;BridgeBio-Pharma-to-Harness-Genetic-Insights-for-the-Discovery-of-Rare-Disease-Therapeutics/default.aspx [SID1234639709]). The goal of the collaboration is to generate new insights focused on genetic modifiers and the discovery of novel therapeutic targets for rare diseases and other unmet medical needs.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The agreement expands upon the longstanding partnership between the two companies to combine the strengths of BridgeBio’s deep expertise in rare disease research and development of therapeutics, and Invitae’s rare disease enriched dataset and analytical capabilities. Invitae has provided clinical testing for more than 4 million patients, generating an extensive dataset that is uniquely positioned to deepen insights on patients with genetic-driven disease.

"Invitae is on a mission to bring comprehensive genetic information into mainstream medicine to improve healthcare for billions of people. By leveraging de-identified genetic information from patients, our researchers can gain a much deeper understanding of the genetic basis of a disease," said W. Michael Korn, M.D., chief medical officer at Invitae. "Through this partnership, we aim to support the development of novel therapeutic targets and advance transformative medicines for patients with rare disease."

Access to large genetic and clinical datasets are needed to advance research and discover novel drug targets and are often hard to find for researchers.

"We chose to partner with Invitae because of the unique scale and depth of their dataset on affected populations. Patients with severe and highly penetrant dominant disorders are not represented in general population studies, making it nearly impossible to find data anywhere except a disease-focused cohort like Invitae’s," said Sun-Gou Ji, Ph.D., vice president of computational genetics at BridgeBio. "These rich data sources will continue to offer researchers a mechanism to get a much deeper understanding of genetic variations and their effect on diseases."

Together Invitae and BridgeBio will translate genetic and phenotypic data into insights to improve therapeutic discovery and design for patients with rare disease. Invitae will analyze longitudinal medical phenotypes in linked genetic and clinical datasets, in order to understand the burden of disease in a real-world setting. Harnessing BridgeBio’s disease expertise, Invitae will leverage AI-based phenotypic clustering to identify subgroups of patients based on their genetic and phenotypic profiles. Invitae will also conduct association testing to identify potential genetic modifiers of disease phenotype, severity, onset and progression.

Immutep Quarterly Activities Report & Appendix 4C Q2 FY24

On January 30, 2024 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported an update on the ongoing development of its product candidates, eftilagimod alpha (efti) and IMP761 for the quarter ended 31 December 2023 (Q2 FY24) (Press release, Immutep, JAN 30, 2024, View Source [SID1234639708]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

EFTI DEVELOPMENT PROGRAM FOR CANCER

TACTI-002 (KEYNOTE-PN798) – Phase II clinical trial in first line NSCLC

Immutep reported excellent new clinical data from the TACTI-002 trial evaluating efti in combination with KEYTRUDA (pembrolizumab) at the ESMO (Free ESMO Whitepaper) Congress in October 2023. A median Overall Survival (OS) of 35.5 months was reported in first line NSCLC patients expressing PD-L1 (TPS ≥1%). Encouragingly, for patients with low PD-L1 expression (TPS 1-49%) median OS was 23.4 months, for patients with negative expression (TPS<1%) median OS was 15.5 months, and a median OS has not yet been reached in patients with high PD-L1 expression (TPS ≥50%).

New biomarker data from the trial was presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in November. The data demonstrated an early increase in immune cells (absolute lymphocyte count) was linked to improved clinical outcomes including OS. Significant increases of Th1 biomarkers (IFN-gamma, CXCL-10) and RNA levels of immune activating genes were observed in patients. Similar immune response biomarkers in the blood were reported previously from Immutep’s double-blind, randomised AIPAC Phase IIb trial, which combined efti with chemotherapy alone and did not include any anti-PD-1 therapy.

TACTI-003 (KEYNOTE-PNC34) – Phase IIb clinical trial in 1st line HNSCC

Enrolment was completed for the TACTI-003 trial in November 2023. A total of 171 first line head and neck squamous cell carcinoma (1L HNSCC) patients have been enrolled in this randomized, multicenter Phase IIb trial evaluating efti in combination with pembrolizumab in 138 patients with PD-L1 positive (Combined Positive Score [CPS] ≥1) tumors (Cohort A) and in 33 patients with PD-L1 negative tumors (Cohort B).

The primary endpoint of the study is ORR of evaluable patients according to RECIST 1.1. Secondary endpoints include OS, ORR according to iRECIST, PFS, and DoR. Patients in Cohort A whose tumors express PD-L1 (CPS >1) are stratified by CPS 1-19 and CPS >20, and the clinical results for these CPS groups, as well as for patients in Cohort B with CPS <1, will be evaluated.

Immutep expects to report first data from TACTI-003 in H1 CY2024.

AIPAC-003 – Integrated Phase II/III trial in Metastatic Breast Cancer

The Company completed the safety lead-in portion of the AIPAC-003 trial evaluating for the first time 90mg of efti in combination with paclitaxel in 6 patients during the quarter. The treatment was well tolerated with no dose limiting toxicities. This good safety profile enabled the lead-in phase to be closed after the first 6 patients. Following the recommendation of the independent Data Monitoring Committee (IDMC), the Company proceeded into the randomized Phase II portion of study and is currently dosing patients. Currently 18 patients have been dosed in the randomized part.

TACTI-004 – Phase III registrational trial in 1L NSCLC

Immutep received constructive regulatory feedback from the Paul-Ehrlich-Institut (PEI), a German regulatory authority and part of the Committee for Medicinal Products for Human Use (CHMP), regarding the planned TACTI-004 trial of efti for 1L NSCLC in December. The PEI is supportive of Immutep moving ahead with the registrational trial evaluating efti in combination with an anti-PD-1 therapy in a chemotherapy-free regimen or as a triple combination approach that includes chemotherapy. Also, the PEI acknowledged the good safety profile of efti in combination with anti-PD-1 therapy.

Additional interactions with the FDA, other local European regulators, as well as with other stakeholders and potential partners are ongoing. Immutep plans to announce the final trial design for TACTI-004 in Q1 of CY2024.

INSIGHT-003 – Phase I in 1L NSCLC

Promising efficacy and tolerability data was presented from the INSIGHT-003 trial at the ESMO (Free ESMO Whitepaper) Congress 2023 in October. The trial evaluates efti plus anti-PD-1 therapy and doublet chemotherapy as first line therapy in non-squamous NSCLC patients. A strong ORR of 71.4% was reported, along with a Disease Control Rate of 90.5% and a 10.1-month median PFS. Median OS has not been reached, despite 81% of patients having low or negative PD-L1 expression.

In the difficult-to-treat PD-L1 TPS <50% patient population (i.e. those with cold or tepid tumors), the triple combination achieved a high 70.6% response rate and median PFS that exceeded 10 months in both low (TPS 1-49%) and negative (TPS<1%) PD-L1 patients, which collectively represent roughly 70% of the overall NSCLC patient population and remain an area of high unmet need.

In November, the INSIGHT-003 trial was expanded to four sites across Germany to support faster enrolment. Currently, 30 out of a total of 50 patients are enrolled. Recruitment is expected to be completed in 1H CY2024.

INSIGHT-005 – Phase I trial in Urothelial Carcinoma

The first patient was enrolled and safely dosed in the investigator-initiated INSIGHT-005 trial, following the close of the quarter in January 2024. The study is evaluating efti and the anti-PD-L1 therapy BAVENCIO (avelumab) in up to 30 patients with metastatic urothelial cancer and is jointly funded with Merck KGaA, Darmstadt, Germany.

EFTISARC-NEO – Phase II Trial in Soft Tissue Sarcoma

The EFTISARC-NEO trial continued throughout the quarter, with 9 patients now enrolled and participating. The study will evaluate efti in combination with pembrolizumab and radiotherapy in up to 40 soft tissue sarcoma (STS) patients in the neoadjuvant (prior to surgery) setting. The trial is funded by a Polish grant program and is the first chemo-free triple combination therapy of efti as well as the first to evaluate the product candidate in a neoadjuvant setting. STS is an orphan disease with high unmet medical need and poor patient prognosis. Currently, Immutep expects first clinical data to be reported in H1 of CY2024.

IMP761 DEVELOPMENT PROGRAM FOR AUTOIMMUNE DISEASE

IMP761 is the Company’s proprietary preclinical candidate and world’s first LAG-3 agonist that aims to treat the underlying cause of multiple autoimmune diseases. Immutep is continuing its pre-clinical development and IND-enabling toxicology studies, which are necessary to evaluate the safety and toxicity of IMP761 before first-in-human trials can begin.

Immutep expects to begin the clinical development of IMP761 by mid-CY2024. Preparations for clinical development are ongoing.

PARTNER UPDATE: MONASH UNIVERSITY

Following the close of the quarter, Immutep entered into a research collaboration agreement with Monash University. The new agreement reflects an extension of the research collaboration agreements with Monash University signed in 2017 and 2020. Importantly, the new agreement will enable the parties to progress their investigations into the structure of LAG-3 and how LAG-3 interacts with its main ligand, MHC Class II. The research continues to be led by Professor Jamie Rossjohn at Monash University and Immutep’s CSO, Dr Frederic Triebel.

INTELLECTUAL PROPERTY

During the quarter, Immutep was granted a new patent for efti by the Korean Intellectual Property Office. The patent protects Immutep’s intellectual property for combination therapies comprised of efti and a chemotherapy agent which is oxaliplatin, carboplatin, or topotecan. The application was filed as a second divisional application and follows the grant of the first divisional patent, announced in 2022.

FINANCIAL SUMMARY

Immutep continued prudent cashflow management and strategic investment into its clinical trial programs for efti and preclinical program for IMP761 during the second quarter (Q2 FY24).

Immutep’s cash position remains very strong with a cash and cash equivalent balance as at 31 December 2023 of approximately $103.7 million. With an expected cash reach till early CY2026, the Company is well financed to reach key milestones that will potentially add value to efti and IMP761.

Cash receipts from customers in Q2 FY24 were $38k, compared to $132k in Q1 FY24. During the quarter, the Company received a $1.1 million cash rebate from the Australian Federal Government’s research and development (R&D) tax incentive program and a €1.6 million (~$2.6 million) R&D tax incentive payment in cash from the French Government under its Crédit d’Impôt Recherche scheme (CIR).

The net cash used in G&A activities in the quarter was $0.8 million, compared to $1.6 million in Q1 FY24.

Payments of $427k to Related Parties (detailed in Item 6 of the Appendix 4C) comprises Non-Executive Directors’ fees and Executive Directors’ remuneration.

The net cash used in R&D activities in the quarter was $6.9 million, compared to $9.7 million in Q1 FY24. The decrease in cash used for the quarter was mainly due to the following:

1)
decreased clinical trial expenses since the TACTI-002 clinical trial is in close out phase;

2)
reduced contract laboratory services compared to last quarter; and

3)
decreased efti manufacturing activity.

Payment for staff costs was $2.2 million in the quarter compared to $2.3 million last quarter.

Total net cash outflows used in operating activities in the quarter were $5.5 million compared to $12.9 million in Q1 FY24.