On November 5, 2024 AnaptysBio, Inc. (Nasdaq: ANAB), a clinical-stage biotechnology company focused on delivering innovative immunology therapeutics, reported financial results for the third quarter ended Sept. 30, 2024 and provided a business update (Press release, AnaptysBio, NOV 5, 2024, View Source [SID1234647720]).

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"We remain confident in the potential best-in-class profiles of our programs targeting BTLA and PD-1 co-inhibitory receptors to drive differentiated results as we approach multiple clinical catalysts and value drivers for Anaptys, including top-line Phase 2b data in AD for ANB032, our BTLA agonist, in December. We’ve also completed enrollment for the Phase 2b trial of rosnilimab, our PD-1 agonist, in RA and are narrowing our guidance for top-line data to February 2025," said Daniel Faga, president and chief executive officer of Anaptys. "Additionally, enrollment in healthy volunteers has commenced for the Phase 1 trial for ANB033, our anti-CD122 antagonist, and we look forward to disclosing the Phase 1b indication in 2025. Looking to the end of the year, we are on track to have four programs in clinical development."

Updates on Wholly Owned ICM Pipeline

ANB032 (BTLA agonist antibody)
•Top-line Week 14 data for global Phase 2b trial in moderate-to-severe AD anticipated in December 2024
◦Enrolled approximately 200 patients in a placebo-controlled trial assessing three dose levels of subcutaneously administered ANB032 (randomized 1:1:1:1) for a 14-week treatment duration and then followed for a six-month off-drug follow-up period on well-established endpoints, including EASI-75 and IGA 0/1
▪Enrollment included approximately 15% of patients with Dupixent/anti-IL-13 treatment experience
•Presented analyses that characterize a BTLA transcriptomic signature in AD at the European Academy of Dermatology and Venerology (EADV) Congress in September 2024
◦Poster presentation is available at View Source
Rosnilimab (PD-1 agonist antibody)
•Top-line Week 12 data for global Phase 2b trial in moderate-to-severe RA anticipated in February 2025
◦Completed enrollment of approximately 420 patients in a placebo-controlled trial assessing three dose levels of subcutaneously administered rosnilimab (randomized 1:1:1:1) for a 12-week treatment duration on well-established endpoints, including DAS28-CRP, CDAI and ACR20/50/70
▪At Week 14, rosnilimab-treated patients who achieve low disease activity, defined as CDAI<=10, are eligible to be dosed for an additional 16-week all-active treatment period and then followed for a three-month off-drug follow-up period
•Enrollment ongoing for global Phase 2 trial in moderate-to-severe ulcerative colitis (UC)

◦132-patient placebo-controlled trial assessing two dose levels of subcutaneously administered rosnilimab (randomized 1:1:1) for a 12-week treatment duration on well-established endpoints, including clinical response on modified Mayo score (mMS), clinical remission on mMS and endoscopic remission
▪Rosnilimab and placebo-treated patients who achieved clinical response on mMS are eligible to continue on their assigned treatment for an additional 12 weeks, while patients on placebo who are non-responders will be crossed over to the high-dose rosnilimab treatment arm, in an all-active treatment period and then followed for a three-month off-drug follow-up period
▪In October 2024, an optional 26-week, blinded treatment extension period (TEP) was implemented for patients who remain in clinical response at Week 24 in the U.S.; EU implementation anticipated in early 2025
◦Top-line Week 12 data anticipated in Q1 2026
•Presented data evaluating the PD-1 depletion and agonism mechanisms of rosnilimab in vitro with UC patient-derived PBMCs and a mouse model of colitis at the 2024 United European Gastroenterology Week (UEGW) in October 2024
◦Poster presentation is available at View Source
ANB033 (anti-CD122 antagonist antibody)
•Phase 1 trial initiated in healthy volunteers in October 2024
◦Phase 1b indication to be disclosed in 2025
ANB101 (BDCA2 modulator antibody)
•Submitted investigational new drug (IND) application and plan to initiate enrollment for Phase 1 trial in healthy volunteers in Q1 2025
Legacy Clinical-Stage Cytokine Antagonist Programs Available for Out-Licensing
•Presented full data from the Phase 3 GEMINI-1 and GEMINI-2 trials of imsidolimab (IL-36R) in generalized pustular psoriasis (GPP) at the EADV Congress in September 2024
◦Poster presentation is available at View Source
•Intend to out-license imsidolimab in 2024
GSK Immuno-Oncology Financial Collaboration
•GSK anticipates top-line data in H1 2025 from COSTAR Lung Phase 3 trial comparing cobolimab, a TIM-3 antagonist, plus dostarlimab, a PD-1 antagonist, plus docetaxel to dostarlimab plus docetaxel to docetaxel alone in patients with advanced NSCLC who have progressed on prior anti-PD-(L)1 therapy and chemotherapy
•GSK anticipates top-line data in Q4 2024 from the FIRST Phase 3 trial for platinum-based therapy with dostarlimab and niraparib versus platinum-based therapy as first-line treatment of Stage III or IV nonmucinous epithelial ovarian cancer
Cash Runway
•Cash and investments of $458.0 million as of September 30, 2024 and reiterating cash runway through year-end 2026

Third Quarter Financial Results
•Cash, cash equivalents and investments totaled $458.0 million as of September 30, 2024, compared to $417.9 million as of December 31, 2023, for an increase of $40.1 million due primarily to the $100.0 million underwritten registered direct offering completed in Q3 and $50.0 million received from the Sagard royalty monetization in Q2 offset by operating activities.
•Collaboration revenue was $30.0 million and $48.2 million for the three and nine months ended September 30, 2024, compared to $3.3 million and $8.2 million for the three and nine months ended September 30, 2023. The increase in non-cash revenue is due to a $15.0 million commercial milestone earned for annual Jemperli sales exceeding $250.0 million and increased royalties recognized for sales of Jemperli.
•Research and development expenses were $42.2 million and $121.3 million for the three and nine months ended September 30, 2024, compared to $30.9 million and $98.8 million for the three and nine months ended September 30, 2023. The increase was due primarily to development costs for rosnilimab, ANB032, ANB033 and ANB101 offset by a decrease in development costs for imsidolimab. The R&D non-cash, stock-based compensation expense was $4.0 million and $10.9 million for the three and nine months ended September 30, 2024, as compared to $2.2 million and $7.7 million in the same period in 2023.
•General and administrative expenses were $10.6 million and $32.2 million for the three and nine months ended September 30, 2024, compared to $10.2 million and $31.7 million for the three and nine months ended September 30, 2023. The G&A non-cash, stock-based compensation expense was $4.2 million and $14.9 million for the three and nine months ended September 30, 2024, as compared to $5.6 million and $17.4 million in the same period in 2023.
•Net loss was $32.9 million and $123.4 million for the three and nine months ended September 30, 2024, or a net loss per share of $1.14 and $4.46, compared to a net loss of $37.3 million and $121.4 million for the three and nine months ended September 30, 2023, or a net loss per share of $1.41 and $4.49.

On November 5, 2024 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported financial results for the third quarter ended September 30, 2024 (Press release, CRISPR Therapeutics, NOV 5, 2024, View Source [SID1234647714]).

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"We continue to make significant progress across our pipeline of in vivo and ex vivo CRISPR-based therapies," said Samarth Kulkarni, Ph.D., Chief Executive Officer and Chairman of CRISPR Therapeutics. "In addition to the continued momentum of CASGEVY’s launch, we are pleased to share that CASGEVY has received regulatory approvals for the treatment of patients 12 years of age and older with SCD or TDT in Switzerland and Canada. In parallel, we remain focused on advancing our portfolio of clinical trials across oncology, autoimmune, diabetes and cardiovascular indications in a capital efficient manner. We look forward to a number of important data catalysts over the next 9-12 months as we advance our portfolio."

Recent Highlights and Outlook

•
Hemoglobinopathies and CASGEVY (exagamglogene autotemcel [exa-cel])
o
CASGEVY has received regulatory approvals for the treatment of patients 12 years of age and older with sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT) in Switzerland and Canada. CASGEVY is also approved in the U.S., Great Britain, the European Union (EU), the Kingdom of Saudi Arabia (KSA), and the Kingdom of Bahrain (Bahrain) for the treatment of both SCD and TDT, and launches are ongoing. CASGEVY is a collaboration product between CRISPR Therapeutics and Vertex Pharmaceuticals, and as part of an amendment to the collaboration agreement in 2021, Vertex now leads global development, manufacturing, regulatory and commercialization of CASGEVY with support from CRISPR Therapeutics.
o
As of mid-October, 45 authorized treatment centers (ATCs) have been activated globally, including centers in all regions where CASGEVY is approved, and approximately 40 patients have already had at least one cell collection across all regions.
o
Vertex announced a reimbursement agreement with NHS England for eligible TDT patients to access CASGEVY. They have also entered into commercial discussions with NHS England to secure access to CASGEVY for eligible patients with SCD.
o
The Italian Medicines Agency (IMA) approved the request for the implementation of an early access program (EAP), for the use of CASGEVY for the treatment of TDT and SCD.
o
Enrollment has been completed in two global Phase 3 studies of CASGEVY in children 5 to 11 years of age with SCD or TDT and the trials are ongoing.
o
CRISPR Therapeutics has two next generation approaches with the potential to significantly expand the addressable population with SCD and TDT. The Company continues to advance its internally developed targeted conditioning program, an anti-CD117 (c-Kit) antibody-drug conjugate (ADC), through preclinical studies. Additionally, the Company has ongoing research efforts to enable in vivo editing of hematopoietic stem cells. This work could obviate the need for conditioning altogether, expand geographic reach, and enable the treatment of multiple additional other diseases beyond SCD and TDT.
•
Immuno-Oncology and Autoimmune Diseases
o
CRISPR Therapeutics’ next generation allogeneic CAR T candidates reflect the Company’s mission of innovating continuously to bring potentially transformative medicines to patients as quickly as possible. Clinical trials are ongoing for the Company’s next generation CAR T product candidates, CTX112 and CTX131, targeting CD19 and CD70, respectively, across multiple indications. CTX112 and CTX131 both contain novel potency edits which can lead to significantly higher CAR T cell expansion and cytotoxicity, potentially representing best-in-class allogeneic CAR T products for these targets.
o
CRISPR Therapeutics announced that it will present a poster from the Company’s ongoing Phase 1 dose escalation study evaluating the safety and efficacy of CTX112, a next-generation CD19 allogeneic CAR T cell therapy, in relapsed or refractory (r/r) CD19-positive B-cell malignancies at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2024 Annual Meeting. The ASH (Free ASH Whitepaper) abstract includes preliminary data on nine high-risk/heavily pretreated lymphoma patients showing an overall response rate (ORR) of 67% across multiple histologies and a complete response rate (CRR) of 44%, with four patients having achieved responses lasting for more than 6 months, including one patient treated at DL1 who remains in complete remission over a year after CTX112 infusion. Concordant with efficacy, pharmacokinetic (PK) data showed rapid cell expansion for CTX112 with many fold improvements in PK compared to the previous generation CTX110 CAR T. No dose limiting toxicities (DLTs) or adverse events (AEs) of graft versus host disease, hemophagocytic lymphohistiocytosis, or grade (Gr) ≥3 infections were observed, in addition to no Gr ≥3 cytokine release syndrome (CRS), or Gr ≥2 immune effector cell associated neurotoxicity syndrome (ICANS). Compared with first generation allogeneic CAR T therapies like CTX110, CTX112 results in better efficacy at lower doses, higher response rates, and improved PK. These data provide the first clinical evidence that disruptions in the genes encoding Regnase-1 and transforming growth factor beta receptor 2 can lead to increased expansion and functional persistence of CAR T cells. The poster presentation will include additional results from the trial.
o
CTX112 is also in a Phase 1 clinical trial in systemic lupus erythematosus (SLE), with the potential to expand into additional autoimmune indications in the future. Early clinical studies conducted by third parties have shown that CD19-directed autologous CAR T therapy can produce long-lasting remissions in multiple autoimmune indications by deeply depleting B cells. The Company’s first generation allogeneic CD19-directed CAR T program has demonstrated effective depletion of B cells in oncology settings, which supports the potential for CTX112 in autoimmune diseases.
o
CTX131 is currently in ongoing clinical trials in solid tumors and hematologic malignancies including T cell lymphomas (TCL). The Company plans to announce an update from the Phase 1 solid tumor trial in 2025. In certain hematologic malignancies such as TCL, allogeneic CAR T approaches may have greater potential to meet the unmet need in this patient population given the patients’ own T cells are not suitable for autologous manufacturing.

•
In Vivo
o
CRISPR Therapeutics has established a proprietary lipid nanoparticle (LNP) platform for the delivery of CRISPR/Cas9 to the liver. The first two in vivo programs utilizing this proprietary platform, CTX310 and CTX320, are directed towards validated therapeutic targets associated with cardiovascular disease.
o
CTX310 is currently in an ongoing Phase 1 clinical trial targeting ANGPTL3 in patients with homozygous familial hypercholesterolemia (HoFH), severe hypertriglyceridemia (SHTG), heterozygous familial hypercholesterolemia (HeFH), or mixed dyslipidemias. Natural loss-of-function mutations in ANGPTL3 are associated with reduced low-density lipoprotein (LDL-C), triglycerides (TG) and atherosclerotic cardiovascular disease (ASCVD) risk without any negative impact on overall health. CRISPR Therapeutics expects to provide an update from this program in 2025.
o
CTX320 is currently in an ongoing Phase 1 clinical trial targeting LPA in patients with elevated lipoprotein(a) [Lp(a)], which has shown to have an independent association with major adverse cardiovascular events (MACE). Up to 20% of the global population has elevated Lp(a) levels. CRISPR Therapeutics expects to provide an update from this program in 2025.
o
The Company continues to advance two additional preclinical programs, CTX340 targeting angiotensinogen (AGT) for the treatment of refractory hypertension and CTX450 targeting 5’ aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias (AHP). CRISPR Therapeutics is conducting IND/CTA-enabling studies and expects to initiate both clinical trials in the second half of 2025.
•
Regenerative Medicine
o
CTX211, an allogeneic, gene-edited, stem cell-derived beta islet cell precursor, is currently in an ongoing Phase 1 clinical trial for the treatment of Type 1 Diabetes (T1D). CRISPR Therapeutics remains committed to its goal of developing a beta-cell replacement product that does not require chronic immunosuppression.
o
Vertex has non-exclusive rights to certain CRISPR Therapeutics’ CRISPR/Cas9 technology to accelerate development of potentially curative cell therapies for T1D. CRISPR Therapeutics remains eligible for development milestones and would receive royalties on any future products resulting from this agreement.
•
Third Quarter 2024 Financial Results
o
Cash Position: Cash, cash equivalents, and marketable securities were $1,935.6 million as of September 30, 2024, compared to $1,695.7 million as of December 31, 2023. The increase in cash was primarily driven by proceeds from the $280.0 million February 2024 registered direct offering, a $200.0 million milestone payment received from Vertex Pharmaceuticals in connection with the approval of CASGEVY, proceeds from employee option exercises as well as interest income, offset by operating expenses.
o
R&D Expenses: R&D expenses were $82.2 million for the third quarter of 2024, compared to $90.7 million for the third quarter of 2023. The decrease in R&D expense was primarily driven by reduced variable external research and manufacturing costs.
o
G&A Expenses: General and administrative expenses were $17.4 million for the third quarter of 2024, compared to $18.3 million for the third quarter of 2023.
o
Collaboration Expense: Collaboration expense, net, was $11.2 million for the third quarter of 2024, compared to $23.4 million for the third quarter of 2023. The decrease in collaboration expense, net, was primarily attributable to the time of reaching the deferral limit on costs related to the CASGEVY program.
o
Net Loss: Net loss was $85.9 million for the third quarter of 2024, compared to a net loss of $112.2 million for the third quarter of 2023.
About CASGEVY (exagamglogene autotemcel [exa-cel])

CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT, in which a patient’s own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene. This edit results in the production of high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. CASGEVY has been shown to reduce or eliminate VOCs for patients with SCD and transfusion requirements for patients with TDT. CASGEVY is approved for certain indications in multiple jurisdictions for eligible patients.

About the CRISPR Therapeutics-Vertex Collaboration

CRISPR Therapeutics and Vertex entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. CASGEVY represents the first potential treatment to emerge from the joint research program. Under an amended collaboration agreement, Vertex now leads global development, manufacturing, and commercialization of CASGEVY and splits program costs and profits worldwide 60/40 with CRISPR Therapeutics. Vertex is the manufacturer and exclusive license holder of CASGEVY.

About CTX112

CTX112 is being developed for both oncology and autoimmune indications. CTX112 is a next-generation, wholly-owned, allogeneic CAR T product candidate targeting Cluster of Differentiation 19, or CD19, which incorporates edits designed to evade the immune system, enhance CAR T potency and reduce CAR T exhaustion. CTX112 is being investigated in an ongoing clinical trial designed to assess safety and efficacy of the product candidate in adult patients with relapsed or refractory CD19-positive B-cell malignancies who have received at least two prior lines of therapy. In addition, CTX112 is being investigated in an ongoing clinical trial designed to assess safety and efficacy of the product candidate in adult patients with system lupus erythematosus.

About CTX131

CTX131 is being developed for both solid tumors and hematologic malignancies, including T cell lymphomas (TCL). CTX131 is a next-generation, wholly-owned, allogeneic CAR T product candidate targeting Cluster of Differentiation 70, or CD70, an antigen expressed on various solid tumors and hematologic malignancies. CTX131 incorporates edits designed to evade the immune system, prevent fratricide, enhance CAR T potency and reduce CAR T exhaustion. CTX131 is being investigated in ongoing clinical trials designed to assess the safety and efficacy of the product candidate in adult patients with relapsed or refractory solid tumors and hematologic malignancies, including TCL.

About In Vivo Programs

CRISPR Therapeutics has established a proprietary lipid nanoparticle (LNP) platform for the delivery of CRISPR/Cas9 to the liver. The Company’s in vivo portfolio includes its lead investigational programs, CTX310 (directed towards angiopoietin-related protein 3 (ANGPTL3)) and CTX320 (directed towards LPA, the gene encoding apolipoprotein(a) (apo(a)), a major component of lipoprotein(a) [Lp(a)]). Both are targeting validated therapeutic targets for cardiovascular disease. CTX310 and CTX320 are in ongoing clinical trials in patients with heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, mixed dyslipidemias, or severe hypertriglyceridemia, and in patients with elevated lipoprotein(a), respectively. In addition, the Company’s research and preclinical development candidates include CTX340 and CTX450, targeting angiotensinogen (AGT) for refractory hypertension and 5’-aminolevulinate synthase 1 (ALAS1) for acute hepatic porphyria (AHP), respectively.

About CTX211

CTX211 is an allogeneic, gene-edited, stem cell-derived investigational therapy for the treatment of type 1 diabetes (T1D), which incorporates gene edits that aim to make cells hypoimmune and enhance cell fitness. This immune-evasive cell replacement therapy is designed to enable patients to produce their own insulin in response to glucose. A Phase 1 clinical trial for CTX211 for the treatment of T1D is ongoing.

On November 5, 2024 Compugen Ltd. (Nasdaq: CGEN) (TASE: CGEN) a clinical-stage cancer immunotherapy company and a pioneer in computational target discovery, reported that data supporting the anti-tumor activity and safety profile of the triple combination COM701, COM902 and pembrolizumab in advanced heavily pre-treated patients with platinum resistant ovarian cancer (PROC) has been published as an abstract released by the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Compugen, NOV 5, 2024, View Source [SID1234647713]).

This data and additional clinical data will be presented by Oladapo Yeku, M.D., Ph.D., FACP, Assistant Professor of Medicine, Harvard Medical School, and Director of Translational Research, Gynecologic Oncology Program, Massachusetts General Hospital, Boston, MA, and an investigator in this study, as a poster presentation at the 39th Annual Meeting of SITC (Free SITC Whitepaper), taking place between November 8-10, 2024 in Houston, Texas.

"The data from this study along with data Compugen previously presented, demonstrate that COM701 is active, has a favorable safety profile, and is a differentiated immune checkpoint inhibitor. COM701 in combination with COM902 (Fc reduced anti-TIGIT) and pembrolizumab (anti-PD-1) resulted in durable objective responses in late-stage ovarian cancer patients typically not responsive to other immunotherapeutic agents," said Dr. Oladapo Yeku. "There is a significant unmet need for effective, durable, and tolerable treatment options for patients with relapsed ovarian cancer. I look forward to discussing this data in Houston at SITC (Free SITC Whitepaper) on Friday, November 8, 2024 and participating in further clinical development of COM701."

Anat Cohen-Dayag, Ph.D. President, and Chief Executive Officer of Compugen added, "We are highly encouraged by the consistency of the data between our two platinum resistant ovarian cancer studies demonstrating COM701 driven activity and safety profile in more than forty advanced and heavily pre-treated patients. We believe these data support our initial observation of the unique mechanism of action of COM701 translating into clinical benefit in patients with ovarian cancer. We are encouraged by feedback from ovarian cancer experts supporting advancing COM701 to an earlier setting of ovarian cancer therapy based on its overall activity, safety profile and durability demonstrated in advanced disease. There is a gap in care for women with platinum sensitive ovarian cancer, who respond to chemotherapy but are ineligible for or cannot tolerate additional maintenance treatment. These patients have a less compromised immune system, providing the opportunity to harness the unique mechanism of action of COM701 to potentially change the disease trajectory improving progression free survival."

Dr. Cohen-Dayag continued, "Our development path in earlier lines of ovarian cancer will start by addressing this unmet need. I look forward to discussing these data and our future development plans including a fireside chat with Dr. Yeku, as part of our third quarter conference call that will take place on November 12, 2024, at 8:30 am ET."

The abstract is now available on the publication section of Compugen’s website. The poster and short video presentation of the poster by Dr. Yeku will be available on the publication section of Compugen’s website on Friday November 8, 2024.

SITC 2024 abstract
Data cut off: May 16, 2024
Note: The poster to be presented at SITC (Free SITC Whitepaper) on November 8, 2024 will include additional data
Treatment
COM701+COM902+pembrolizumab
No. patients
23 (efficacy evaluable)
Confirmed ORR
17.4% (1 CR, 3 PR)
Confirmed DCR
43.5%
Immune activation
Increase in peripheral IFNγ
Safety
Majority AEs GR ≤2
No GR 4/5 AEs
1 GR 3 event, serious immune related encephalopathy resolving following treatment with steroids

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On November 5, 2024 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported two presentations featuring bezuclastinib at the 66th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) being held December 7-10, 2024 in San Diego, California (Press release, Cogent Biosciences, NOV 5, 2024, View Source [SID1234647712]).

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The first presentation will describe long term follow-up from patients in Part 1 of the ongoing APEX trial. APEX is a global, open-label, multi-center, two-part Phase 2 clinical trial evaluating the safety, efficacy, pharmacokinetic and pharmacodynamic profiles of bezuclastinib in patients with Advanced Systemic Mastocytosis (AdvSM).

The second presentation will describe long term follow-up from patients who participated in the Open Label Extension portion of the ongoing SUMMIT trial. SUMMIT is a randomized, double-blind, placebo-controlled, global, multicenter Phase 2 trial evaluating bezuclastinib in patients with Nonadvanced Systemic Mastocytosis (NonAdvSM).

Details for the presentations are as follows:

Apex Part 1: Updated Assessment of Bezuclastinib (CGT9486), a Selective KIT D816V Tyrosine Kinase Inhibitor, in Patients with Advanced Systemic Mastocytosis (AdvSM)
Session Name: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Advancing Treatment Paradigms in Myeloproliferative Neoplasms and Mastocytosis
Presenter: Daniel J. DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute and Professor of Medicine, Harvard Medical School
Session Date and Time: Sunday, December 8, 2024, 4:30 PM – 6:00 PM PT (7:30pm – 9:00pm ET)
Presentation time: 5:30pm PT (8:30pm ET)
Publication Number: 659
Location: Manchester Grand Hyatt, San Diego Grand Hall D

Updated Efficacy and Safety Results of Patients Receiving Selected 100mg Bezuclastinib Dose and Participating in the Open-Label Extension of Summit: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial of Bezuclastinib in Adult Patients with Nonadvanced Systemic Mastocytosis
Presenter: Lindsay Rein, MD, Associate Professor of Medicine in the Division of Hematologic Malignancies and Cellular Therapy at Duke University
Session Name: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster III
Session Date and Time: Monday, December 9, 2024, 6:00 PM – 8:00 PM PT (9:00pm-11:00pm ET)
Publication Number: 4556
Location: San Diego Convention Center Halls G-H

Full abstracts are available for online viewing via the ASH (Free ASH Whitepaper) Annual Meeting website: View Source

Investor Webcast Details
Cogent will host a webcast on Monday, December 9, 2024 at 8:00am ET (5:00am PT) led by Cogent’s President and CEO, Andrew Robbins which will include a review of the SUMMIT and APEX data presentations by Daniel J. DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute and Professor of Medicine, Harvard Medical School. The speakers and additional members of Cogent leadership will be available during the Question and Answer session.

The live webcast will be accessible on the Investors and Media page of Cogent’s website at investors.cogentbio.com/events. After completion of the event, an archived replay will also be available.

On November 5, 2024 Century Therapeutics, Inc. ("Century", NASDAQ: IPSC), an innovative biotechnology company developing induced pluripotent stem cell (iPSC)-derived cell therapies in immuno-oncology and autoimmune disease, reported financial results and business highlights for the third quarter ended September 30, 2024 (Press release, Century Therapeutics, NOV 5, 2024, View Source [SID1234647711]).

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"Broadening our strategic focus in autoimmune indications to include idiopathic inflammatory myopathy and diffuse cutaneous systemic sclerosis will give us greater insight into the potential of CNTY-101 in an underserved therapeutic category that we believe is uniquely suited to allogeneic iNK cell therapies. Our confidence in the application of CNTY-101 in autoimmune diseases continues to be reinforced by the Phase 1 ELiPSE-1 trial in patients with r/r B-cell lymphomas where updated interim data shows increased overall response rates at higher doses and observations of deepening responses with additional cycles, alongside a continued favorable safety profile," said Brent Pfeiffenberger, Pharm.D., Chief Executive Officer of Century Therapeutics. "The advancement of our pre-clinical pipeline across multiple cell types is similarly promising, as highlighted by what we believe to be the industry-first presentation of iPSC-derived CD4+ and CD8+ CAR T cells that demonstrate αβ-like T cell function at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Building on this progress, we are conducting a strategic review of Century’s pre-clinical pipeline and expect to announce the outcome in the first quarter of 2025. We have recently refined our organizational structure to enhance ongoing efficiencies and program alignment. On behalf of everyone here at Century, I’d like to thank departing colleagues for their important contributions to building the company’s programs and technology. Supported by extended cash runway from these changes, we remain focused on execution in the period ahead and look forward to delivering our next set of potential catalysts."

Research & Development Highlights

· Consistent with Century’s commitment to expand investigation of autoimmune disease indications during the second half of 2024, the company recently amended the Phase 1 CALiPSO-1 trial of CNTY-101 (NCT06255028) and Investigational New Drug (IND) application to include evaluation of idiopathic inflammatory myopathy (IIM) and diffuse cutaneous systemic sclerosis (dcSSc). This builds upon earlier alignment with the U.S. Food and Drug Administration to expand clinical development to lupus nephritis (LN) in addition to systemic lupus erythematosus (SLE). With the implementation of this amendment, CALiPSO-1 consists of a basket protocol study design, with four arms designed to evaluate the safety and preliminary efficacy of CNTY-101. The study will enroll participants ≥17 years old with refractory B-cell-mediated autoimmune diseases following an inadequate response to at least two lines of prior standard of care immunosuppressive therapies, now including those with moderate to severe IIM and dcSSc with treatment-resistant and active disease alongside those with moderate to severe SLE with or without LN. Century has activated multiple clinical sites in the United States, and expects to activate additional sites in the coming months, with ability to enroll patients across indications. To further facilitate enrollment, the company plans to expand trial sites to select European countries. Century will provide updated timing on initial clinical data from CALiPSO-1 once a clear cadence of patient enrollment has been established across indications.

· Updated interim clinical data from Century’s ongoing Phase 1 ELiPSE-1 study evaluating CNTY-101 (NCT05336409) in relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) has shown increased overall response rates at higher doses and observations of deepening responses with additional cycles alongside a favorable safety profile, building on encouraging interim data previously presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. As of the data snapshot October 15, 2024, eight additional participants have been treated with CNTY-101 for a total of 20 participants evaluable for safety and 19 for preliminary efficacy. Treatment with CNTY-101 continued to be safe and generally well tolerated with no dose-limiting toxicities reported, no additional cases of immune effector cell-associated neurotoxicity syndrome (ICANS), and no Grade 3 or higher cytokine release syndrome (CRS). Consistent with the manageable safety profile observed to date, a majority of participants received CNTY-101 infusions in an outpatient setting. Dose level DL3B (1 billion cells in each of three weekly doses per cycle), which represents the largest single trial cohort (n=6), has shown an overall response rate (ORR) of 83% and a complete response rate (CRR) of 33%, with all participants receiving additional cycles of treatment.

A dose-dependent increase in CNTY-101 exposure was observed as evaluated by a novel pharmacokinetics cell-free DNA (cfDNA) method for detecting total body presence of CNTY-101. Preliminary cfDNA data from Schedule B (three weekly CNTY-101 infusions per cycle) showed that in cycles starting with lymphodepletion, a similar level of exposure was observed between the first and third infusion when the patients’ endogenous T and NK cells had recovered. This supports persistence upon repeated cell dosing, consistent with the anticipated protective activity of Century’s proprietary Allo-Evasion technology.

Efficient B-cell depletion was observed in all participants treated with CNTY-101 who had measurable circulating B cells at baseline. Evaluable re-emergent B cells (N=4 participants) were enriched for naive subtypes with minimal class-switched memory subsets detected. This profile in re-emergent B cells has been associated with SLE responses after CD19 cell therapy treatment, which we believe further supports application of CNTY-101 in the CALiPSO-1 study. Based on favorable safety and encouraging early efficacy data at DL3B, Century is proceeding with DL4B (3 billion cells in each of three weekly doses per cycle), and recently treated the first participant at this dose. The company expects to provide updated clinical data by mid-2025.

Further details pertaining to the ELiPSE-1 data update can be found in Century’s corporate presentation housed on the investor relations section of the website.

· Century separately announced the acceptance of five poster presentations at the upcoming 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting to be held in San Diego, CA from December 7-10, 2024. The presentations include demonstration of pre-clinical function comparable to autologous T cells by allogeneic iPSC-derived CD4+ and CD8+ CAR T cells, alongside additional innovations that highlight the engineerability of the iPSC-derived immune effector cells, a core benefit of the company’s platform. These include data from advanced CAR endo-domains that improved cytotoxicity and persistence, enhanced Allo-Evasion via a novel CD300a TASR that demonstrated universal protection from NK cells, and differentiation stage specific promoters that allow for selective control of gene expression.

Business Highlights

· Following the integration of Clade Therapeutics, Century is conducting a strategic review of the pre-clinical pipeline to leverage the unique capabilities and technologies at Century towards high-value and differentiated programs. The company expects to conclude and communicate the results of this review in the first quarter of 2025. As part of this review, in October, Century implemented changes to the organization structure including elimination of overlapping technical and research capabilities to enhance ongoing efficiencies and alignment with the company’s key programs. With these changes, Century has extended expected cash runway into the second half of 2026.

· In September 2024, Century announced the appointments of Morgan Conn, Ph.D., as Chief Financial Officer and Chad Cowan, Ph.D., as Chief Scientific Officer. The company also announced the transition of Hy Levitsky, M.D., President of Research and Development, from operational duties to serve as an advisor to Century.

Third Quarter 2024 Financial Results

· Cash Position: Cash, cash equivalents, and marketable securities were $244.7 million as of September 30, 2024, as compared to $261.8 million as of December 31, 2023. Net cash used in operations was $85.9 million for the nine months ended September 30, 2024, compared to net cash used in operations of $62.1 million for the nine months ended September 30, 2023.

· Collaboration Revenue: Collaboration revenue generated through the company’s collaboration, option, and license agreement with Bristol-Myers Squibb was $0.8 million for the three months ended September 30, 2024, compared to $0.1 million for the same period in 2023.

· Research and Development (R&D) expenses: R&D expenses were $27.2 million for the three months ended September 30, 2024, compared to $22.8 million for the same period in 2023. The increase in R&D expenses was primarily due to progression of the ELiPSE-1 trial and start-up costs of the CALiPSO-1 trial, increased manufacturing activity for CNTY-101, and the acquisition of Clade Therapeutics.

· General and Administrative (G&A) expenses: G&A expenses were $8.4 million for the three months ended September 30, 2024, compared to $9.0 million for the same period in 2023.

· Net loss: Net loss was $31.2 million for the three months ended September 30, 2024, compared to $32.7 million for the three months ended September 30, 2023.

Financial Guidance

· The company expects full year generally accepted accounting principles (GAAP) operating expenses to be between $150 million and $160 million.

· The company estimates its cash, cash equivalents, and investments will support operations into the second half of 2026.