Celeritas Insights

Vertex Pharmaceuticals ($VRTX)

Summary

Vertex Pharmaceuticals announced the early FDA approval of Alyftrek, its fifth medicine for cystic fibrosis (CF), which offers once-daily dosing and improved efficacy compared to Trikafta.
The company is on track with its "five-in-five" strategy, aiming for five product launches within five years, with Exa-Cel for sickle cell disease and transfusion-dependent beta thalassemia expected to contribute to revenue diversification.
Vertex is expanding its clinical trials and product offerings into new disease areas, including myotonic dystrophy type 1, autosomal dominant polycystic kidney disease, and type 1 diabetes, with multiple late-stage programs in development.
The company is preparing for the launch of suzetrigine, a NAV1.8 inhibitor for acute pain, with a PDUFA action date set for January 30, 2025, and is focused on ensuring broad access and distribution.
Vertex is advancing its renal portfolio, with ongoing Phase III trials for primary APOL1-mediated kidney disease and plans to initiate a trial for autosomal dominant polycystic kidney disease this year.
Povetacicept, a treatment for IgA nephropathy, is in a global Phase III study, with expectations for accelerated approval based on interim analysis results anticipated this year.
The company is also working on neuropathic pain treatments, with ongoing Phase III studies and plans to optimize clinical trial designs to address the high unmet need in this area.
Vertex has established partnerships, including a collaboration with Zai Lab to bring povetacicept to the Chinese market, where there is a high prevalence of IgA nephropathy.

Upcoming catalysts

January 30, 2025: PDUFA action date for suzetrigine in acute pain.
2025: Completion of enrollment in the interim analysis cohort for inaxaplin in AMKD.
2025: Completion of enrollment in the interim analysis cohort for povetacicept in IgAN.
2025: Completion of enrollment and dosing for zimislecel in type 1 diabetes.
2025: Data release for VX522, mRNA program for cystic fibrosis.
2025: Data release for VX264 program in type 1 diabetes.
2025: Initiation of Phase II proof of concept study for VX407 in autosomal dominant polycystic kidney disease.

Intellia Therapeutics ($NTLA)

Summary

Intellia Therapeutics is advancing three Phase III clinical programs: NTLA-2002 for hereditary angioedema (HAE) and NTLA-2001 for transthyretin amyloidosis (ATTR), both expected to launch between 2027 and 2030.
NTLA-2002 is anticipated to be the first product launched, with a potential "functional cure" for HAE, allowing patients to be free from attacks and chronic therapy.
The HAELO study for NTLA-2002 is expected to be fully enrolled by the end of 2025, with results anticipated in 2026.
NTLA-2001 is being studied in two parallel trials (MAGNITUDE for cardiomyopathy and MAGNITUDE 2 for polyneuropathy), with over 550 cardiomyopathy patients expected to be enrolled by year-end 2025.
The company has received several regulatory designations that facilitate accelerated reviews for its breakthrough products.
Intellia is focusing on operational excellence and clinical work completion as it prepares for commercialization, with a goal to submit a Biologics License Application (BLA) for NTLA-2002 in 2026.
The market for HAE and ATTR is substantial, with physician interest in NTLA-2002 and NTLA-2001 being high due to their efficacy and simplified treatment regimens.
The company has made strategic decisions to prioritize HAE and ATTR programs, setting aside other projects to concentrate resources on these near-term value-creating opportunities.

Upcoming catalysts

Late 2025: Completion of enrollment for the HAELO study of NTLA-2002 for hereditary angioedema (HAE).
Late 2025: Updated data from Phase I and II studies of NTLA-2002.
Early 2026: Phase III HAELO results for NTLA-2002.
2026: Substantially completed enrollment for the MAGNITUDE study for NTLA-2001 (ATTR cardiomyopathy).
2026: Completion of enrollment for the MAGNITUDE 2 study for NTLA-2001 (ATTR polyneuropathy).
Late 2026: Planning for the first BLA submission for NTLA-2002.
2027: Expected launch of NTLA-2002 for HAE.

Sarepta Therapeutics ($SRPT)

Summary

Sarepta Therapeutics reported strong financial performance, with total net product revenue of $1.788 billion in 2024, exceeding guidance by over $100 million.
Elevidys, the company's gene therapy for Duchenne muscular dystrophy, generated $384 million in Q4 2024, marking a 112% increase from the previous quarter and a total of $821 million for the year.
The company has dosed over 600 patients with Elevidys, including a significant number of non-ambulatory patients, and plans to expand its addressable patient population by targeting antibody-positive boys.
Sarepta is advancing its limb-girdle muscular dystrophy programs, with a BLA submission for SRP-9003 expected in 2025 and ongoing trials for SRP-9004 and SRP-9005.
The company has entered a partnership with Arrowhead Pharmaceuticals to develop a new siRNA platform, which includes four clinical-stage programs and three preclinical programs targeting various neuromuscular and pulmonary diseases.
Upcoming milestones include readouts for FSHD and DM1 trials in the second half of 2025, as well as IND filings for new gene therapy programs.
Sarepta's strategic plan, "Sarepta 2030," aims to establish the company as a leading biotech focused on rare diseases, with projected cumulative revenue of $30 billion by 2030, including contributions from limb-girdle programs.
The company reported no permanent denials for therapy due to reimbursement issues.

Upcoming catalysts

Q1 2025: Start of registration trial for SRP-9005.
H2 2025: Readout for FSHD program from siRNA platform.
H2 2025: BLA submission for SRP-9003.
H2 2025: Readout for DM1 program from siRNA platform.
2025: Readout of two-year data from EMBARK trial for Elevidys.
2025: Filing of IND for Huntington's disease program.
2025: Filing of IND for gene therapy for limb-girdle type 2A.
2025: R&D day to present new research and development work.

Alnylam Pharmaceuticals ($ALNY)

Summary

Alnylam is anticipating the approval of vutrisiran for ATTR cardiomyopathy, which could establish a flagship franchise for the company.
Global regulatory filings following positive results from the Phase III sHELIOS-B study.
Alnylam is advancing its pipeline with nucresiran, which has shown promising Phase I data for annual or biannual dosing.
The company has initiated a Phase II study for vutrisiran in early-onset Alzheimer's disease and is progressing with zilebesiran in hypertension.
Alnylam plans to launch vutrisiran in 2025, with a PDUFA date set for March 23, 2025.
The company aims to deliver over 25 clinical programs by the end of 2025, focusing on RNAi therapeutics across multiple tissue types.
Alnylam is guiding for combined product sales of $2.05 billion to $2.25 billion in 2025, indicating strong growth potential.
The company is set to present additional insights on its R&D pipeline at an upcoming R&D Day in February 2025.

Upcoming catalysts

March 23, 2025: PDUFA date for vutrisiran in ATTR Cardiomyopathy.
Q1 2025: Additional insights on pipeline programs at R&D Day in February.
H1 2025: Initiation of Phase III ATTR-CM study for nucresiran.
H2 2025: Phase II KARDIA-3 study results for zilebesiran in hypertension.
H2 2025: Phase II study initiation for ALN-6400 in bleeding disorders.
H2 2025: Expected vutrisiran launches in Germany and Japan.

Wave Life Sciences ($WVE)

Summary

Wave Life Sciences has made significant advancements in RNA editing, particularly with the first examples of human RNA editing in Alpha-1 antitrypsin patients, showing promising protein levels that replicate those seen in heterozygous populations.
The company has filed multiple Clinical Trial Applications (CTAs) for its INHBE program targeting obesity, with plans to initiate the study in Q1 2025.
This program aims to provide a novel, long-acting, muscle-sparing approach to obesity treatment.
Wave has demonstrated best-in-class treatments for Huntington's disease, achieving the first allele-specific silencing in humans and positive interim data for WVE-N531, with results expected in Q1 2025.
The ongoing clinical study for WVE-006 (Alpha-1 antitrypsin deficiency) has completed multi-dosing in healthy volunteers, with multi-dose data anticipated in 2025.
The company is also advancing its PNPLA3 program for genetic liver disease, with plans to enter the clinic in 2026, and is exploring upregulation of LDLR to address hypercholesterolemia.
Wave is on track to deliver 48-week data for DMD (Duchenne Muscular Dystrophy) in Q1 2025, with expectations for regulatory feedback and potential accelerated registration.
The company is planning a registrational study for Huntington's disease, utilizing caudate atrophy as a primary endpoint, with IND submission expected in the second half of 2025.
Wave anticipates significant growth in its pipeline, with an addressable patient population exceeding 100 million across its various therapeutic areas.

Upcoming catalysts

Q1 2025: Initiate Phase I study for WVE-007 in obesity.
Q1 2025: 48-week dystrophin data and regulatory feedback regarding accelerated approval for WVE-N531 in DMD.
2025: Multi-dose data presentation for WVE-006 in Alpha-1 Antitrypsin Deficiency.
H2 2025: IND submission for Huntington's Disease (HD) study using caudate atrophy as a primary endpoint.
2026: Anticipated initiation of clinical trials for PNPLA3 and LDLR programs.

CRISPR Therapeutics ($CRSP)

Summary

CRISPR Therapeutics has one approved therapy, CTX001, for sickle cell disease and beta thalassemia, and is actively expanding its clinical pipeline with five programs currently in clinical trials across various disease areas, including oncology and autoimmune diseases.
The company is focusing on enhancing CTX001's profile through gentler conditioning agents and in vivo gene delivery, aiming to broaden its patient population.
CRISPR is advancing its CAR-T programs CTX112 and CTX131, targeting both oncology and autoimmune diseases, with promising early data indicating high response rates in heavily pre-treated patients.
The company is also developing in vivo therapies targeting cardiovascular diseases (CTX310 and CTX320) and anticipates data updates in the first half of 2025.
CTX001 has received FDA approval and is now available in eight jurisdictions, with over 50 authorized treatment centers established globally, indicating strong market interest and support.
CRISPR is exploring innovative approaches in diabetes treatment by engineering stem cells into functional islet cells, with ongoing programs CTX211 and CTX213.
The company is positioned for a catalyst-rich year in 2025, with multiple clinical readouts expected across its pipeline, including updates on CTX112 and in vivo therapies.
The company is actively pursuing business development opportunities to enhance its pipeline and capabilities, leveraging its strong financial position with $1.9 billion in cash.

Upcoming catalysts

H1 2025: Initial data from CTX310 for cardiovascular disease.
H1 2025: Initial data from CTX320 for elevated LPA.
Mid-2025: Update on CTX112 CAR-T in oncology and autoimmune disease.
Late 2025: Update on CTX131 CAR-T for solid tumors and T-cell malignancies.
2025: Update on diabetes programs CTX211 and CTX213.
2025: Update on CTX450 for acute hepatic porphyrias.

Prime Medicine ($PRME)

Summary

Prime Medicine is advancing its Prime Editing platform, focusing on programs for chronic granulomatous disease (CGD), Wilson's disease, and cystic fibrosis.
Prime Medicine's PASSAGE technology is being integrated into all development programs, enhancing the precision of gene editing.
Prime Medicine is developing a proprietary universal lipid nanoparticle (LNP) delivery system, which has shown promising preclinical results in liver programs.
Initial clinical data for PM359 in CGD is anticipated later this year, marking a significant milestone as it will be the first-ever clinical data for Prime Editing.
A strategic collaboration with Bristol-Myers Squibb (BMS) has been established to develop ex vivo T-cell therapies, with a total potential value of $3.5 billion.
IND enabling studies for the Wilson's disease program PM577 were initiated in November 2023, with plans to file an IND or CTA in 1H 2026 and report clinical data in 2027.
For cystic fibrosis, Prime Medicine is pursuing two approaches: hotspot editors to cover multiple mutations and the PASSAGE technology for precise gene replacement.

Upcoming catalysts

Late 2025: Initial clinical data from PM359 trial for CGD.
H1 2026: IND or CTA filing for PM577 in Wilson's disease program.
2026: Pivotal study for PM359 in CGD.
2026: In vivo data from cystic fibrosis programs.
2027: Pivotal data from CGD program.
2027: Clinical data from Wilson's disease program.

Beam Therapeutics ($BEAM)

Summary

Beam Therapeutics is advancing its base editing platform, which allows for precise genetic modifications without causing double-stranded breaks in DNA, potentially leading to safer and more effective therapies.
The company is actively enrolling patients in its BEACON trial for BEAM-101, targeting severe sickle cell disease, with over 40 patients enrolled and 13 doses delivered to date.
They anticipate reaching the 30th patient by mid-2025, which could set the stage for a BLA filing.
BEAM-101 has shown promising early results, including rapid neutrophil and platelet engraftment, efficient cell collection, and a favorable safety profile, with patients achieving a protective fetal hemoglobin to sickle globin ratio indicative of non-disease status.
BEAM-301, targeting glycogen storage disease 1A, is set to begin dosing the first patient in early 2025, following successful preclinical results.
A study for BEAM-302, aimed at treating alpha-1 antitrypsin deficiency, is now open for enrollment in four different markets, with first clinical data expected in the first half of 2025.
The ESCAPE program is in development, aiming to use an antibody conditioning agent (BEAM-103) instead of chemotherapy for sickle cell disease, with preclinical studies showing promising engraftment results in non-human primates.
The company is collaborating with Apellis and Pfizer on various programs, including a gene editing approach to modify the neonatal FC receptor for autoimmune disorders, currently in late preclinical studies.
The company has established GMP manufacturing capabilities and has completed over 100 batches at its North Carolina facility, enhancing its operational readiness for clinical trials.

Upcoming catalysts

Early 2025: First patient dose for BEAM-301 in Glycogen Storage Disease Type 1A.
Mid-2025: 30th patient dosing in BEAM-101's BEACON trial.
Mid-2025: Updated BEAM-101 data presentation at EHA.
H1 2025: Initial data from BEAM-302 trial for Alpha-1 Antitrypsin Deficiency.
Late 2025: Phase I study for BEAM-103 (antibody conditioning).

Arcturus Therapeutics ($ARCT)

Summary

Arcturus has received approval for its first product, Kostaive, in Japan, with a positive CHMP opinion for European approval expected in Q1 2025.
The company is advancing two key preclinical programs: LUNAR-OTC for ornithine transcarbamylase deficiency and LUNAR-CF for cystic fibrosis, with interim data readouts anticipated in the first half of 2025.
The Kostaive vaccine utilizes self-amplifying mRNA technology (STARR), which has shown superior immune responses in clinical trials compared to conventional mRNA vaccines.
Arcturus has partnered with CSL for its vaccine enterprise, with a profit-sharing agreement and commercial milestones tied to European approval.
The H5N1 vaccine program, funded by BARDA, has initiated a Phase I trial, with the first subject treated in December 2024.
The company has received multiple designations from the FDA and European Commission for its pipeline assets, including orphan drug and fast track designations.
Arcturus has established a manufacturing presence in Japan, supported by significant government grants, to facilitate the production of its vaccines.
2025 is positioned as a pivotal year for Arcturus, with multiple key clinical data readouts and potential regulatory approvals on the horizon.

Upcoming catalysts

Q1 2025: Full EMA approval for Kostaive in Europe.
H1 2025: Interim data readout from ARCT-810 Phase II trial for LUNAR-OTC in Ornithine Transcarbamylase Deficiency.
H1 2025: Interim data readout from ARCT-032 Phase II trial for LUNAR-CF in Cystic Fibrosis.
H2 2025: Phase I interim data readout for LUNAR-H5N1 vaccine.
Early 2025: BLA filing for Kostaive in the US.

Sana Biotechnology ($SANA)

Summary

Sana has demonstrated the ability to transplant allogeneic pancreatic islets into a type 1 diabetes patient without immunosuppression, marking a significant milestone in cellular therapy.
The company is developing SC451, a therapy aimed at providing a single treatment for type 1 diabetes that allows patients to maintain normal blood glucose levels without insulin or immunosuppression.
SC291 is being developed for B-cell-mediated autoimmune diseases, with the goal of resetting the immune system to allow patients to live without symptoms or medications.
The company is also advancing SC262, targeting patients who have failed CD19 CAR-T therapies, with ongoing human testing and promising early results.
The GLEAM study, a Phase I trial for SC291 in lupus and ANCA-associated vasculitis, has received fast-track designation and is currently enrolling patients.
The company has successfully shown deep B-cell depletion in an oncology setting, which they aim to translate into clinical benefits for autoimmune diseases.
Sana is focused on overcoming the challenges of manufacturing and scaling their therapies, with a goal of creating a GMP-compliant master cell bank for future clinical applications.
The company is optimistic about the potential of their hypoimmune platform to provide curative therapies across various diseases, including type 1 diabetes and autoimmune conditions.

Upcoming catalysts

Date not specified: Data update from the GLEAM study (Phase I study for lupus and ANCA-associated vasculitis).
Date not specified: Data presentation from the SC262 trial (Phase I study targeting patients who have failed CD19 CAR-T cells).

Editas Medicine ($EDIT)

Summary

Editas Medicine has transitioned to a pure in vivo gene editing company, focusing on functional upregulation of disease-mitigating genes using CRISPR technology.
The company reported a 100% complete response rate in treated patients with its Reni-cel ex vivo therapy for sickle cell disease and beta-thalassemia, validating its treatment strategy.
Editas has demonstrated high levels of in vivo editing of HBG1 and HBG2 genes in hematopoietic stem cells using its proprietary lipid nanoparticle (LNP) delivery platform, achieving approximately 40% editing efficiency.
The company is expanding its targeted LNP platform to include additional cell types, enhancing its therapeutic potential and addressing a broader range of diseases.
A collaboration with Genovant was announced to access liver-tropic LNPs, showing proof of concept for high-efficiency genome editing in the liver.
Editas plans to declare two in vivo development candidates for the treatment of beta thalassemia and sickle cell disease by mid-2025 and aims to submit at least one IND application by mid-2026, with human clinical trials expected to begin in the second half of 2026.
Editas has extended its cash runway into Q2 2027, supported by recent non-dilutive financing and partnerships that validate its intellectual property and scientific approach.

Upcoming catalysts

Mid-2025: Declaration of two in vivo development candidates for beta thalassemia and sickle cell disease.
Mid-2025: Announcement of a third targeted tissue or cell type.
H1 2026: Submission of at least one IND.
H2 2026: Initiation of at least one human clinical trial.
Late 2026: Expected human in vivo proof of concept data.
Late 2027: Potential initiation of pivotal studies.

Verve Therapeutics ($VERV)

Summary

Verve Therapeutics is focused on developing in vivo gene editing medicines aimed at cardiovascular disease.
The company has two clinical programs currently in progress: VERVE-102 targeting PCSK9 and VERVE-201 targeting ANGPTL3, with a third program, VERVE-301 targeting LPA, recently advancing to candidate nomination.
VERVE-102 is in a Phase I trial (HEART-2) for patients with heterozygous familial hypercholesterolemia (HEFH) and premature coronary artery disease, with initial data expected in Q2 2025.
The trial has progressed to the 0.6 mg/kg dosing cohort, with no serious adverse events reported thus far.
A collaboration with Eli Lilly allows for potential opt-in to the VERVE-102 program, with a decision expected in the second half of 2025.
VERVE-201 is currently in the PULSE-1 Phase I trial for refractory hypercholesterolemia, with updates anticipated in the second half of 2025.
The company has demonstrated proof of concept for durable LDL reduction with VERVE-101, showing sustained LDL lowering for up to 18 months post-treatment.
The market for cholesterol-lowering therapies remains largely untapped, with only 30-40% of HEFH patients and less than 5% of eligible ASCVD patients currently receiving PCSK9 inhibitors.
The company anticipates a milestone-rich 2025, with key data releases and potential advancements in their clinical programs.

Upcoming catalysts

Q2 2025: Initial data release from the HEART-2 clinical trial for VERVE-102.
H2 2025: Final data for the dose escalation portion of the HEART-2 clinical trial.
H2 2025: Delivery of opt-in package to Eli Lilly for VERVE-102 with potential decision by year-end.
H2 2025: Initiation of Phase II clinical trial for VERVE-102.
H2 2025: Program update for VERVE-201 targeting ANGPTL3.

Allogene Therapeutics ($ALLO)

Summary

The company has three key pipeline assets: ALLO-501A (CD19 CAR), ALLO-329 (dual-targeting CD19 and CD70), and ALLO-316 (CD70 CAR for solid tumors).
ALLO-501A is currently in a pivotal Phase II study (ALPHA3) targeting MRD-positive patients with large B-cell lymphoma, with interim analysis expected in mid-2025.
ALLO-329 is designed for autoimmune disorders, with preclinical data suggesting superior efficacy compared to traditional CD19 CARs and is expected to enter clinical trials by year-end 2025.
ALLO-316 is focused on renal cell cancer, showing a 50% overall response rate in patients with CD70-positive tumors, with further data updates anticipated in mid-2025.
The company emphasizes the scalability of its allogeneic CAR-T manufacturing process, capable of treating over 60,000 patients annually.
Allogene aims to transition CAR-T treatments from specialized centers to community-based cancer centers, enhancing accessibility for patients.
The ALPHA3 study design includes a control arm and aims to establish the efficacy of ALLO-501A in a first-line setting, potentially leading to a BLA filing in 2027 if results are positive.
The company is strategically positioning itself in the MRD setting, which is gaining traction in treatment guidelines, to maintain a competitive edge against other CAR-T therapies.

Upcoming catalysts

Q1 2025: IND for ALLO-329.
Mid-2025: Phase I trial initiation for ALLO-329.
Mid-2025: First interim analysis of the ALLO-501A program to determine lymphodepletion regimen.
Mid-2025: Update on ALLO-316 Phase IB data presentation.
Late 2025: Proof of concept data for ALLO-329 expected by year-end.
H1 2026: Complete patient enrollment and first interim efficacy analysis of the ALLO-501A program focusing on event-free survival.
Late 2026: Primary analysis of the ALLO-501A program.
2027: Potential BLA submission for ALLO-501A.

By Sakis Paliouras, PhD

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