Regeneron Provides Update on Biologics License Application for Linvoseltamab

On August 20, 2024 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for the Biologics License Application (BLA) for linvoseltamab in relapsed/refractory (R/R) multiple myeloma (MM) that has progressed after at least three prior therapies (Press release, Regeneron, AUG 20, 2024, View Source [SID1234646033]). This anticipated outcome was previously disclosed during Regeneron’s second quarter 2024 earnings call.

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The sole approvability issue identified is related to findings from a pre-approval inspection at a third-party fill/finish manufacturer for another company’s product candidate. The third-party fill/finish manufacturer has since informed Regeneron that it believes the findings have been resolved, their facility is awaiting reinspection by the FDA, and it is expected to take place in the coming months.

Regeneron is committed to working closely with the third-party fill/finish manufacturer and the FDA to bring linvoseltamab to appropriate patients with R/R MM as quickly as possible, which is critical because most MM patients relapse and ultimately require additional therapies in late-line settings.

Regulatory review of linvoseltamab remains ongoing by the European Medicines Agency (EMA) in the same indication. Linvoseltamab is investigational, and its safety and efficacy have not been approved by any regulatory authority.

InnoCare Releases 2024 Interim Results and Business Highlights

On August 20, 2024 InnoCare Pharma (HKEX: 09969; SSE: 688428), a leading biopharmaceutical company focusing on cancer and autoimmune diseases, reported the 2024 interim results and corporate update as of 30 June 2024 (Press release, InnoCare Pharma, AUG 20, 2024, View Source [SID1234646022]).

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Revenue of orelabrutinib increased by 30.0% year-on-year (YoY) to RMB417.0 million in the first half of 2024, with a YoY growth of 48.8% in the second quarter. This is attributed to the rapid growth of marginal zone lymphoma (MZL) as well as effective sales execution.
The Loss decreased by 37.6% YoY to RMB268.0 million in the first half of 2024.
Cash and Related Accounts Balance stood at about RMB7.99 billion as of 30 June 2024. This robust cash position provides the Company with flexibility to expedite clinical development and invest in a competitive pipeline.
Gross Profit increased by 19.3% to RMB359.6 million in the first half of 2024. Gross profit margin was 85.7%, representing an increase of 5.8 percentage points, which was primarily due to the sales combination change of drugs and service.
Research and Development Expenses increased by 17.5%1 to RMB420.8 million in the first half of 2024 primarily due to mainly due to more resources to increased investment in advanced technology platform innovation and Phase III clinical trials aimed at accelerating the Group’s transformation.
Total Revenue reached RMB419.7 million in the first half of 2024, which was primarily attributable to rapid ramp-up of orelabrutinib sales volume. All three approved indications of orelabrutinib, including relapsed and refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (r/r CLL/SLL), relapsed and refractory mantle cell lymphoma (r/r MCL) and relapsed and/or refractory marginal zone lymphoma (r/r MZL) have been covered under the updated National Reimbursement Drug List (NRDL) 2023. Orelabrutinib has been approved as the first and only BTK inhibitor for r/r MZL in China. Orelabrutinib was officially included as a class I recommended regimen for the treatment of r/r MZL patients in the 2024 Chinese Society of Clinical Oncology (CSCO) Guidelines. The Company’s commercial capabilities have undergone significant enhancements, including an optimized and upgraded commercial team, which has developed more executable strategies. The dedicated team has been optimized to operate with heightened efficiency and strategic focus, ensuring effective execution of market initiatives. This optimization has bolstered the team’s ability to penetrate markets swiftly and effectively. These advancements underscore InnoCare’s commitment to delivering value and driving sustainable growth in the Company’s commercial endeavors.

Benefiting Patients Worldwide

Entering InnoCare version 2.0, the Company is continuing to strengthen the entire value chain and rapidly advance the clinical trials of its pipeline. Over the next three to five years, five to six innovative drugs are expected to be approved for marketing, addressing unmet treatment needs and benefiting patients worldwide.

Becoming a Leading Player in Hemato-Oncology

Hemato-oncology, including lymphoma, leukemia, and myeloma, is known for its high mortality rates. InnoCare is dedicated to developing therapeutics with diverse mechanisms of action (MoA) to achieve comprehensive coverage of blood tumor indications, with the aspiration of becoming a leader in this field.

Beyond the approved indications, InnoCare is advancing the first line registrational clinical trials and new drug application (NDA) for orelabrutinib. Tafasitamab (CD19 monoclonal antibody), another key product, is expected to be approved for marketing in the first half of next year, further strengthening the Company’s market presence. InnoCare is also accelerating the development of BCL2 inhibitor ICP-248, which has significant combination synergy with orelabrutinib. Notably, BCL2 inhibitors are the preferred therapeutic option following resistance to BTK inhibitors, creating an optimal sequential treatment strategy. With these assets in the pipeline, along with the molecule glue ICP-490, monoclonal antibody ICP-B05 and bispecific antibody ICP-B02, and potential future developments from internal and external sources, the Company is aimed at becoming a leading player in hemato-oncology both in China and worldwide.

Orelabrutinib

The clinical trial of orelabrutinib in combination with ICP-248, a BCL2 inhibitor developed by InnoCare, for first-line treatment of CLL/SLL was initiated in May of this year, and patient enrollment of the Phase II trial has been completed as of this announcement.
The Company is accelerating the registrational trials and NDA of the first line indications of orelabrutinib, including CLL/SLL, SCL and diffuse large B-cell lymphoma (DLBCL).
Orelabrutinib continues to gain attention from top international academic conferences. Five studies of orelabrutnib were selected for the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024, with a prospective study of orelabrutinib regimen in treatment-naive MZL as an oral presentation at the conference. 10 studies on orelabrutinib have been selected for the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress.
Tafasitamab

The biologics license application (BLA) for tafasitamab in combination with lenalidomide for adult patients with r/r DLBCL who are not eligible for Autologous Stem Cell Transplant (ASCT) was accepted and granted priority review in China in June 2024. DLBCL is the most common type of non-Hodgkin’s lymphoma (NHL), accounting for 31%~34% of NHL patients globally. In China, DLBCL accounts for 45.8% of all NHLs2.
Tafasitamab regimen was approved by the Department of Health, the Hong Kong Special Administrative Region, China, and approved for use in Bo’ao and Greater Bay Area with first prescription issued respectively.
ICP-248

ICP-248 is a novel, orally bioavailable BCL2 selective inhibitor. The clinical trial of ICP-248 in combination with orelabrutinib for first line (1L) CLL/SLL was initiated, and patient enrollment for the Phase II trial has been completed.
So far, 47 patients have been dosed, and among 28 evaluable patients with BTK inhibitor failure r/r MCL, the overall response rate (ORR) was 71.4%.
The investigational new drug (IND) filing for ICP-248 for Acute Myeloid Leukemia (AML) has been accepted by the CDE.
ICP-490

Developed from InnoCare’s molecular glue platform, ICP-490 shows strong potential to revolutionize the treatment of MM, NHL, and other hemato-oncology indications, whether as a monotherapy or in combination with other therapies.
The Phase I dose escalation study is ongoing in China with multiple myeloma (MM) and NHL patients, demonstrating a good tolerability and safety profile. This safety profile has supported the decision to continue dose escalation to the next dosage level.
ICP-B02 (CM355)

ICP-B02 is a CD20xCD3 bispecific antibody co-developed with Keymed. Data from both the intravenous infusion (IV) and the subcutaneous (SC) formulations have shown good efficacy of ICP-B02 in patients with follicular lymphoma (FL) and DLBCL. All 15 patients who were treated with ICP-B02 at doses ≥6mg achieved response, resulting in an ORR of 100%. All patients who achieved CR maintained the remission as of the cutoff date.
Based on the encouraging results of ICP-B02 as a single agent, the Company is planning for a dose expansion study of ICP-B02 in combination with other immunochemotherapies targeting earlier lines of treatment in NHL patients. The IND application for the combination therapies was approved in China in June 2024.
ICP-B05 (CM369)

ICP-B05 (CM369) is a potential first-in-class anti-CC chemokine receptor 8 (CCR8) monoclonal antibody, co-developed by InnoCare and Keymed as a monotherapy or in combination with other therapies for the treatment of various cancers.
The Phase I trial is ongoing, aiming to evaluate the safety, tolerability, pharmacokinetic characteristics, and efficacy of ICP-B05 in subjects with advanced solid tumors and r/r NHL.
Preliminary efficacy was observed in NHL patient. ICP-B05 was well tolerated with no dose-limiting toxicities (DLTs).
Advancing Research and Development in Solid Tumors

InnoCare strives to expand the breadth of its pipeline to cover solid tumor diseases areas through a combination of targeted therapy and immune-oncology approaches. The Company believes that potential best-in-class molecule, zurletrectinib (ICP-723), will enable InnoCare to establish a solid footprint in the field of solid tumor treatment. To benefit a broader range of patients, InnoCare’s rapidly maturing early-stage pipeline, including the cornerstone therapy ICP-189 and ICP-B05 immune-oncology treatment, aims to offer competitive treatment solutions for a large array of solid tumors, both in China and worldwide.

Zurletrectinib (ICP-723)

The fusion mutation of NTRK gene is a carcinogenic factor for many cancers, including lung cancer, colorectal cancer, breast cancer, pancreatic cancer and melanoma. Zurletrectinib is a second generation TRK inhibitor developed by InnoCare. The Company is accelerating the registrational trial of zurletrectinib in China, which has entered the pre-NDA stage.
Zurletrectinib has demonstrated good efficacy and safety profile. It was shown to overcome acquired resistance to the first generation TRK inhibitors, bringing hope for patients who failed prior TRKi therapy.
The clinical study with zurletrectinib has covered neurotrophic tyrosine receptor kinase (NTRK) gene fusion adult patients, adolescent patients (12 to 18 years old) and pediatric patients (2 to 12 years old). The efficacy has been observed in both adolescent and pediatric patients. The dose escalation trial for pediatric patients has been completed.
ICP-189

The novel SHP2 allosteric inhibitor, ICP-189, is being developed for the treatment of solid tumors as a single agent and/or in combination with other antitumor agents. The clinical trial of the combination of InnoCare’s lCP-189 with ArriVent’s third generation EGFR inhibitor furmonertinib in patients with advanced non-small cell lung cancer (NSCLC) is ongoing, with the preliminary efficacy observed. NSCLC is the predominant subtype of lung cancer, accounting for approximately 85% of all cases3.
Preliminary efficacy was observed in ICP-189 monotherapy. As a potential first-in-class SHP2 inhibitor, ICP-189 is an ideal partner for combination with multiple targeted and immune-oncology therapies in solid tumors. ICP-189 has demonstrated significant anti-tumor effect in tumor models driven by KRASG12C mutation and Epidermal Growth Factor Receptor (EGFR) over-expression. The SHP2 combination therapy provides a promising treatment option for NSCLC patients who are resistant to the third generation EGFR inhibitors.
As of this announcement, the study of the 120mg QD group has been completed, with no DLT observed, and it has shown a favorable PK profile with a long half-life. The patient enrollment at 160mg QD is ongoing.
InnoCare is also actively exploring preclinical development in solid tumors, and developing small molecule and large molecule innovative drugs by building a differentiated platform for the treatment of solid tumors such as lung cancer and gastric cancer, so as to meet huge unmet medical needs.

Comprehensive Coverage in Autoimmune Diseases

Autoimmune diseases can affect almost every organ in the body and can occur at any age. The global market for autoimmune disease therapeutics anticipated to reach $185 billion by 20294. The Company has fortified its powerful discovery engine focusing on global frontier targets for the development of differentiated autoimmune therapeutics through B-cell and T-cell pathways, aiming to offer first-in-class or best-in-class treatments to the massive unmet medical needs with promising market potential worldwide and/or regionally.

Orelabrutinib

ITP: The Company has achieved proof of concept (PoC) for orelabrutinib in the treatment of primary immune thrombocytopenia purpura (ITP), and has completed enrollment of over 50% of patients in the Phase III registrational trial. The annual incidence rate of adult ITP is about 2-10 per 100,000 people5. Only about 70% of patients respond to first-line treatment. Orelabrutinib has potential to provide a better treatment option for ITP patients6. From blood tumor to autoimmune diseases in the hematological field, orelabrutinib will demonstrate its huge commercial potential. The ITP Phase II result was published by the American Journal of Hematology in April 2024. For details, please refer to View Source
SLE: The Phase IIa trial for systemic lupus erythematosus (SLE) demonstrated positive results, with remarkable SLE Responder Index (SRI)-4 response rates observed in a dose dependent manner, along with trends indicating a reduction in proteinuria levels. Orelabrutinib is global first and only BTK inhibitor ever shown efficacy in Phase II SLE trials. A Phase IIb trial is ongoing, and the patients enrollment has been nearly completed as of this announcement.
SLE is a systemic disease that often leads to damage to organs, especially the kidneys and nervous system, skin, blood system, respiratory system, and almost all systems may be affected. According to Frost Sullivan analysis, it is expected that there will be 8.18 million SLE patients worldwide by 2025. The Chinese Systemic Lupus Erythematosus Development Report 2020 points out that there are about one million SLE patients in China, ranking first in the world in number of patients and second in incidence rate.

ICP-332

ICP-332 is a novel tyrosine kinase 2 (TYK2) inhibitor that is being developed for the treatment of various T-cell related autoimmune disorders, including atopic dermatitis (AD), vitiligo, inflammatory bowel disease, etc., with broad market prospects.
The latest data of ICP-332 for the treatment of patients with moderate-to-severe AD has been released at the 2024 American Academy of Dermatology (AAD) Annual Meeting as a late-breaking oral presentation.
ICP-332 achieved multiple efficacy endpoints in the China Phase II study for the treatment of patients with moderate-to-severe AD, demonstrating an outstanding efficacy and safety profile. ICP-332 showed better efficacy profile across different classes/MoAs of therapies for the treatment of AD patients (not a head-to-head comparison).
In the ICP-332 80 mg once-daily (QD) and 120 mg QD groups for four weeks, the response rates of EASI 90 (improvement of at least 90% in EASI score from baseline) and NRS (Pruritus Numerical Rating Scale) score from baseline ≥4 points demonstrated a 40% and 56% improvement respectively compared with the placebo group, both of which were superior to competitors.
ICP-332 was safe and well tolerated in AD patients. The overall incidence rates of adverse events (AEs) in the two treatment groups were comparable to that of the placebo group.
The Company expects to start the patient enrollment of the Phase III trial for AD in China in the fourth quarter of 2024, and to submit IND for the Phase II/III trial for a second indication of vitiligo. The US trials have been initiated.
ICP-488

Data shows that 100 million people worldwide are affected by various types of psoriasis7. ICP-488 is a potent and selective TYK2 allosteric inhibitor that binds to the pseudo kinase JH2 domain of TYK2 and blocks IL-23, IL12, type 1 IFN, and other cytokine receptors. The Phase II study of ICP-488 in psoriasis has completed patient enrollment in May 2024. The Company expects the data readout by the end of 2024.
A total of 129 patients were enrolled in this study. Patients were randomly assigned to two treatment groups and placebo group, for 12 consecutive weeks of treatment.
ICP-488 demonstrated good efficacy and safety in the Phase I study of ICP-488 in psoriasis patients.
Novel Small Molecule Inhibitor of IL-17

IL-17 is a pro-inflammatory cytokine that plays an important role in immune functional responses. Orally administered small molecules targeting IL-17 may represent a convenient alternative to IL-17-targeting monoclonal antibodies for patients. This novel orally available small molecule can potently block the binding of both IL-17AA and IL-17AF to IL-17R.
Dr. Jasmine Cui, the Co-founder, Chairwoman and CEO of InnoCare, said, "In the first half of 2024, our commercial team exceeded pre-set goals, with a significant increase in revenue. We have developed innovative drugs with huge unmet medical needs, with three NDAs submitted in the first half of this year. We have also been actively exploring preclinical innovation, laying a solid foundation for future development. Looking ahead to the second half of the year, we will continue to make concerted efforts in the fields of new drug R&D, clinical development, commercialization and globalization, focusing on key goals to achieve high-quality development."

To know more about the detailed financial data and business updates of InnoCare 2024 annual results, please log in to View Source .

Conference Call Information

InnoCare will host a conference call at 9:30 a.m. Beijing time on August 21 in Chinese and at 8:30 p.m. Beijing time in English on August 21, 2024. Participants must register in advance of the conference call. Details are as follows:

For English conference call, please register through the below link:
View Source

For Chinese conference call, please register through the below link:
View Source

Talus Bioscience Announces $11.2M in New Funding Led by Two Bear Capital to Advance AI Platform for Transcription Factor Therapeutic Discovery

On August 20, 2024 Talus Bioscience, a drug discovery company founded by a world-class team of scientific leaders in proteomics, biochemistry, and machine learning, reported $11.2M in new venture funding (Press release, Talus Bioscience, AUG 20, 2024, View Source [SID1234646021]). The Seed+ round was led by Two Bear Capital, with participation from WRF Capital, NFX, YC Continuity Fund, Funders Club VC, and BoxOne Ventures.

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The funding will be invested to advance Talus Bio’s therapeutic programs, which include Brachyury-driven cancers and an undruggable transcription factor implicated in prostate cancer. It will also accelerate the expansion of the company’s proprietary Multiplexed Assays for the Rational Modulation Of Transcription Factors (MARMOT) platform.

MARMOT leverages new AI models trained on Talus Bio’s dataset for transcription factor activity, currently the largest in the world. MARMOT allows scientists to rapidly identify optimal candidates from billions of compounds, replacing time-consuming high-throughput screens, which have historically failed for transcription factors and are limited to millions of compounds. With MARMOT, machine learning models discover and optimize modulators for any given transcription factor target, enabling the massive acceleration of discovery screening in live, unmodified human cells where targets fold and function properly.

"This new funding from our exceptional partners validates and supports our work producing the first AI model to discover and optimize new modulators of any transcription factor," said Talus Bioscience CEO and Co-Founder Alex Federation, PhD. "With our growing team of leading data scientists, we can use tens of millions of data points generated from the MARMOT platform to predict the best places to look for new molecules to block disease-causing transcription factors. We’re just getting started as we source new partners to help advance the dozens of promising transcription factor candidates we have discovered to date."

Transcription factors are proteins that regulate the genome by binding to DNA and orchestrating which genes are turned on or off at any given time. When they go awry, they often drive cancer and other disease processes like diabetes, inflammatory diseases, fibrosis, and neurological conditions.

"Talus Bio’s platform incorporates advances in chemistry, proteomics and computational biology to generate a dataset that was previously impossible. The scale, comprehensiveness, and efficiency with which they can target transcription factors gives their AI approach a distinct advantage and has already generated a robust list of hits against attractive drug targets," said Avery Sonnenberg, PhD, Principal at lead investor Two Bear Capital. "We’re thrilled to be working with this exceptional team as they pursue both partnerships and internal development of these exciting programs which have the potential to redefine how we treat complex diseases and improve patient outcomes globally."

EMulate Therapeutics Inc. Announces Publication of Pre-Clinical Mouse Model Demonstrating Direct Evidence of Immune Checkpoint Receptor Knock-Down in a Mouse Glioblastoma Model

On August 20, 2024 EMulate Therapeutics, Inc. ("Emulate") reported the Open Journal of Biophysics (OJBIPHY), publisher of over 200 peer-reviewed open access journals, has accepted its manuscript, titled "Magnetic Field Emulations of Small Inhibitor RNA: Effects on Implanted GL261 Tumors in C57BL/6 Immune Competent Mice" for publication (Press release, EMulate Therapeutics, AUG 20, 2024, View Source [SID1234646020]). This submission supports independent results in an animal model of Glioblastoma Multiforme (GBM), recently published by Mukthavaram et al. (Bioelectron Med 2024 Vol. 10 Issue 1 Pages 10), which demonstrates the ability of EMulate’s second signal treatment offering, A2. GBM is a rare brain glioma that currently has no established treatment on the market and is categorized by the U.S. Food and Drug Administration (FDA) as a highly underserved orphan disease (affects fewer than 200,000 in the U.S.). View Source

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The paper demonstrates EMulate’s A2 signal treatment targets the established immune checkpoint inhibitor targets of CTLA-4 and PD-1, reducing the expression of these immune system receptors and inhibiting the growth of tumors in a validated mouse model of GBM. These results support the observed outcomes from a Phase I clinical trial (NCT02507102) demonstrating safety and possible efficacy against GBM in humans.

"The results of this pre-clinical animal model study continue to demonstrate the potential of our ulRFE technology in the treatment of cancers and other challenging diseases with high unmet medical needs. We strongly believe in the potential benefits of this treatment in patients afflicted by cancer with these genetic targets, which we intend to confirm in future clinical trials," stated Xavier Figueroa, Ph.D., EMulate’s SVP of Pre-Clinical Development.

BerGenBio Collaborates with Tempus to Potentially Accelerate Development in STK11m Non-Small Cell Lung Cancer

On August 20, 2024 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, reported a collaboration with Tempus, a technology company leading the adoption of AI to advance precision medicine and patient care, to advance the clinical development of BerGenBio’s selective AXL inhibitor bemcentinib in first line (1L) Non-Small Cell Lung Cancer (NSCLC) patients with STK11 mutations (STK11m) (Press release, BerGenBio, AUG 20, 2024, View Source [SID1234646019]). BerGenBio’s on-going BGBC016 Phase 1b/2a trial is designed to assess the benefit of adding bemcentinib to the current standard of care treatment (immunotherapy + doublet chemotherapy) in 1L STK11m patients, a population with poor outcomes and no specific therapies today.

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The collaboration will provide BerGenBio with access to a tailored cohort of Tempus’ real-world clinical and molecular data that is intended to establish a synthetic control to provide a contextual benchmark for BerGenBio’s innovative study, which aims to address the urgent medical need for effective treatments in STK11m NSCLC patients. Tempus’ comprehensive, AI-enabled platform will enable BerGenBio to receive customized analyses of Tempus data and gain deeper insights into the genomic landscape and therapeutic responses of NSCLC patients with STK11m.

Upon conclusion of the BGBC016 study, the parties intend to present insights derived from the resulting data to appropriate regulatory agencies as a next step in the further development of bemcentinib.

Martin Olin, CEO of BerGenBio, expressed enthusiasm about the collaboration, stating, "We are excited to partner with Tempus to harness the power of their advanced technology in our mission to improve outcomes for NSCLC patients with STK11 mutations. By integrating Tempus’ platform into our study, we aim to enhance our understanding of the disease biology and treatment outcomes, ultimately driving our ability to accelerate further development of bemcentinib".

"We are excited to collaborate with BerGenBio to accelerate the development of precision therapies for STK11m NSCLC patients," said Kate Sasser, Chief Scientific Officer at Tempus. "Together, we aim to unlock new insights that will ultimately improve patient outcomes and redefine the standard of care in this challenging disease setting."