Companies
What's expected at ASH?
Arcellx will reveal the latest results of its lead asset, CART-ddBCMA. To date, data from its Phase 1 CART-ddBCMA trial in relapsed or refractory multiple myeloma show that the median DoR, PFS, and OS have not been reached at a medium follow-up of 22 months after CART-ddBCMA infusion. The therapy also continued to be well-tolerated, with no observed delayed neurotoxicities or Parkinsonian symptoms. At ASH, Arcellx will be presenting updated data from this trial, with a median follow-up of 26.5 months.
In June, the FDA implemented a hold on the Phase 2 iMMagine-1 study investigating CART-ddBCMA in multiple myeloma due to a death; however, this was later lifted in August and was attributed to limitations on bridging therapy in place in the trial protocol. The FDA has since signed off on an updated trial protocol to address this. Arcellx now expect CART-ddBCMA to launch in 2026, with Chairman and CEO Rami Elghandour in November re-iterating the group’s belief in the therapy’s “best-in-class potential” based on its safety and efficacy profile. CART-ddBCMA is forecast to hit sales of $307m in 2028 (50/50 split between Gilead and Arcellx).
It will face a crowded market. J&J’s BCMA-targeting CAR-T therapy Carvykti is forecast to be the market leader, with $3.8 billion in projected 2028 sales. Other competitors in relapsed or refractory multiple myeloma include Bristol Myers Squibb’s Abecma, plus Janssen’s bispecific antibodies Tecvayli and Talvay, and Pfizer’s recently approved Elrexfio. These off-the-shelf therapies don’t require T-cell collection, making them less cumbersome and expensive to administer. Tecvayli is forecast to sell $2.0 billion in 2028.
See our data highlights for Arcellx on the next page.
Arcellx (ACLX) is a Maryland based biotechnology company focused on development of immunotherapies for patients with cancer and other incurable diseases.
IPO Details
IPO in February 2022 (NASDAQ), raising $142m
What’s it worth today?Market Cap (Nov 2023)
$2.5bn
What is the 2028 Sales Forecast?
$234m
MomentumCAGR (2023-2028)
15%
Specialist Subject: Clinical
Oncology & Immunomodulators
Specialist Subject: Technology
Cell therapy
Key Asset(s)
CART-ddBCMA. A gene-modified cell therapy for multiple myeloma. Due to launch in 2026, this asset is expected to account for 85% of Arcellx's sales in 2028. Phase 1 data update at ASH.
In the Pipeline?
Research projects: 5
Preclinical: 1
Phase 1: 2
Phase 2: 1
Phase 3: 0
Dealmaking Highlights
Gilead (50/50 US co-dev/comm deal)In December 2022, Gilead in-licensed WW rights from Arcellx to co-develop and co-commercialise CART-ddBCMA for the treatment of multiple myeloma. Both companies share 50/50 profit in the USA and Arcellx receives royalties in ex-USA regions. In November 2023, this deal was expanded to include lymphomas.Also in November, Gilead’s Kite exercised an option to negotiate access to additional autologous CAR-T cell therapies, concurrent with a $200m equity investment in Arcellx at $61.68/share, and an $85m upfront cash payment.
Through the expanded BCMA cell therapy deal, Kite is buying the rights for ACLX-001, an early phase BCMA-targeting CAR-T cell therapy, for the treatment of multiple myeloma. ACLX-001 is designed using Arcellx's ARC-SparX platform, which comprises of Arcellx's universal ARC-T cells and specialised SparX proteins, and is designed to make cell therapies more dosable, controllable, and adaptable. The deal is seen as a big boost for Arcellx, validating the ARC-SparX platform and giving Gilead a potential replacement for its own CAR-T programmes for multiple myeloma, which it terminated in December 2022.
Regeneron will present new and updated data across six investigational medicines, including pivotal trials results for its lead blood cancer candidate, the CD20xCD3 bispecific antibody odronextamab. The company will share Phase 2 data from the ELM-2 pivotal trial in relapsed/refractory follicular lymphoma (R/R FL) and R/R diffuse large B-cell lymphoma (R/R DLBCL), and Phase 1 data from the ELM-1 trial in R/R DLBCL patients who have progressed after CAR-T therapy.
Primary endpoint results and longer follow-up data from the pivotal Phase 2 LINKER-MM1 trial of BCMAxCD3 targeting linvoseltamab will also feature at the conference.
Regeneron believes that both bispecifics stand apart from competitors Tecvayli (J&J) and recently-approved Elrexfio (Pfizer). For linvoseltamab in particular, that differentiation could result from potentially lower rates of severe cytokine release syndrome (CRS) and thus lower hospitalisation burden. The therapy may also be dosed every four weeks if a good partial response is achieved at the six-month mark.
Regeneron reported high rates of treatment-emergent adverse events, particularly Grade 3 or higher CRS, in prior studies with both assets. The FDA placed a clinical hold on odronextamab in December 2020 over safety concerns. Such adverse effects are, however, common to all CD3-based bispecific activity; any reduction in CRS rates would be an advantage.
Regeneron is initiating studies of both assets in earlier setting, where it believes most of the revenue opportunity lies. Odronextamab is projected to reach worldwide sales of $160m in 2028, including $83 million outside China, Hong Kong, Macau, and Taiwan, where Regeneron retains commercialisation rights.
See our data highlights for Regeneron on the next page.
Summary
Regeneron Pharmaceuticals (REGN) is a New York based biotechnology company focused on development & marketing of medicines for the treatment of eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, pain, hematologic conditions, infectious diseases, and rare diseases.
IPO in April 1991
$85.8bn
$15.8bn
4%
Oncology, Sensory Organs, Systemic Anti-infectives, Immunomodulators
Monoclonal antibodies, gene therapy
Odronextamab - Phase 2. A CD20 x CD3 bispecific antibody being evaluated for relapsed/refractory follicular lymphoma and relapsed/refractory diffuse large B-cell lymphoma. Filed at FDA and EMA, with an FDA target action date of March 31, 2024. Linvoseltamab - Phase 2. BCMA x CD3 bispecific antibody for heavily pre-treated multiple myeloma.
In the pipeline?
Research projects: 9
Preclinical: 17
Phase 1: 14
Phase 2: 17
Phase 3: 7
Zai Labs: odronextamabIn April 2020, Regeneron and Zai Lab announced a strategic collaboration agreement for the development and commercialisation of odronextamab. Regeneron received a $30m upfront payment and is eligible to receive up to $160m in additional regulatory and sales milestones. In exchange, Zai Lab will contribute to global development costs and obtained the rights to develop and exclusively commercialise odronextamab in mainland China, Hong Kong, Taiwan, and Macau. Zai Lab will also make payments to Regeneron based on net sales. Linvoseltamab was developed through a joint venture agreement made with Sanofi in 2015 to discover and develop new immunooncology treatments. In 2019, the deal was re-jigged to give Sanofi opt-in rights to linvoseltamab and a MUC16 x CD3 program, but two years later it declined both, leaving Regeneron with exclusive development and commercialisation rights.
Long-term data for marketed CAR-T cell therapy Yescarta in relapsed/refractory large B-cell lymphoma (R/R LBCL) across three lines of therapy, including overall survival data from the ZUMA-7 trial in patients aged 65+.
Real-world data for marketed CAR-T Tecartus in adult R/R B-cell acute lymphoblastic leukaemia (ALL) and R/R mantle cell lymphoma (MCL). Yescarta is projected to sell $2.6bn in 2028, with $603m for Tecartus.
Gilead stated in their Q3 earnings call that despite strong clinical data, only 10% of eligible 2L LBCL patients in the US are currently treated with a cell therapy, leaving significant room to increase adoption. The company is working on further shortening their 16-day median turnaround treatment? time in the US, which they state is already industry-leading. Main competitors to Yescarta in LBCL are Novartis' Kymriah and Bristol Myers Squibb's Breyanzi.
The CAR-T cell therapy class is undergoing extra scrutiny from the FDA, which on November 28, 2023 announced an investigation into reports of T-cell malignancies in patients who have received BCMA- or CD19-directed genetically modified autologous CAR-T cell immunotherapies such as – but not limited to – Yescarta and Tecartus. These reports were received from clinical trials and post-marketing adverse events data sources. Although the risk of developing secondary malignancies with this class of therapy is already stated in US prescribing information, the FDA is now evaluating the need for regulatory action.
See our data highlights for Gilead on the next page.
Gilead Sciences (GILD) is a California based pharmaceutical company focused on development of therapies for life-threatening diseases & unmet medical needs in virology, oncology & other therapeutic areas.
IPO in January 1992
$92.8bn
$32.1bn
Oncology, Systemic Anti-infectives, Immunomodulators
Small molecules, monoclonal antibodies, cell therapy
Key Haematology Asset(s)
Yescarta and Tecartus - Marketed. CD19-directed CAR-T cell therapies approved for a variety of blood cancers.
Research projects: 27
Preclinical: 26
Phase 1: 38
Phase 2: 22
Arcellx Cell TherapyGilead are continuing to expand their cell therapy portfolio through deals with Arcellx (see Arcellx's section).
Vertex will present updated Phase 3 clinical trial data for exa-cel as a one-time functional cure for sickle cell disease and transfusion-dependent beta thalassemia. Additional presentations will cover quality of life metrics.
FDA granted exa-cel priority review for sickle cell disease and standard review for transfusion-dependent beta thalassemia, with PDUFA dates of December 8, 2023 and March 30, 2024, respectively. EMA is also reviewing the therapy.
The UK approval is currently restricted to patients 12 years and older, though Vertex continues to enroll patients in two global Phase 3 studies in patients between 5 to 11 years. The company is also working on preclinical assets that allow gentler conditioning for exa-cel, which could further broaden the eligible patient population. During Vertex's Q3 earnings call, Vertex's CEO, Stuart Arbuckle, referred to exa-cel as a "multibillion dollar opportunity" and stated that Vertex are on-track in the US and Europe with regards to their supply network and launch preparations.
Analysts forecast $2.8bn in exa-cel sales by 2028 which will be split 60/40 between Vertex and CRISPR Therapeutics. Key competitors include bluebird bio's gene therapies lovo-cel for sickle cell disease and Zynteglo for transfusion-dependent beta thalassemia. bluebird bio abandoned the European market in 2021 due to pricing challenges it encountered with Zynteglo.
See our data highlights for Vertex on the next page.
Vertex Pharmaceuticals (VRTX) is a Massachusetts based pharmaceutical company focused on the development & commercialising medicines for serious diseases.
IPO in July 1991
$89.4bn
$13.8bn
7%
Respiratory, CNS, Endocrine, Musculoskeletal
Small molecules, gene editing
Exa-cel - Phase 3. An autologous, ex vivo CRISPR/Cas9 gene-edited cell therapy being evaluated for sickle cell disease or transfusion-dependent beta thalassemia. Exa-cel (branded Casgevy) received conditional approval in the UK in November, becoming the first CRISPR-edited therapy.
Research projects: 14
Preclinical: 9
Phase 1: 9
Phase 2: 9
CRISPR TherapeuticsExa-cel was developed through a four-year collaboration with CRISPR Therapeutics, signed in 2015. In April 2021, Vertex and CRISPR Therapeutics amended the deal, with Vertex covering 60% of program costs and eligible for 60% of worldwide profits, and CRISPR Therapeutics taking the other 40%.
In September 2022, Vertex licensed non-exclusive clinical and commercial rights to MaxCyte's cell engineering tools including its Flow Electroporation technology, used in exa-cel’s development.
Detailed data from the Phase 3 MANIFEST-2 study investigating pelabresib in myleofibrosis. In a press release on November 20, 2023, MorphoSys reported that the trial had met its primary endpoint: in JAK inhibitor-naive patients, pelabresib in combination with the JAK inhibitor ruxolitinib demonstrated statistically significant and clinically meaningful improvements in the proportion of patients achieving at least a 35% reduction in spleen volume at week 24 (SVR35) compared to placebo plus ruxolitinib. Key secondary endpoints also favoured pelabresib plus ruxolitinib.
However, the MANIFEST-2 study fell short on a key secondary endpoint, 50% reduction in total symptom score (TSS50). This was achieved by 52% of patients in the pelabresib plus ruxolitinib arm at week 24, compared with 46% in the placebo plus ruxolitinib arm (p = 0.216). Throughout pelabresib's development, MorphoSys had stated that statistically significant improvements in both SVR35 and TSS50 at week 24 would be key to attaining regulatory approval. Following a Type C FDA meeting in September 2023, M added a new key secondary endpoint….hoping this might help it gain approval.
Based on the MANIFEST-2 results, MorphoSys stated that the company intends to file for the approval of pelabresib plus ruxolitinib in the US and Europe in mid-2024. If approved, pelabresib is projected to hit $145m in sales in 2028.
See our data highlights for MorphoSys on the next page.
MorphoSys (MOR) is a Germany based biotechnology company focused on development of therapeutic antibodies for the treatment of cancer, rheumatoid arthritis and Alzheimer’s disease.
IPO in March 1999
$732m
$794m
24%
Oncology
Monoclonal antibodies, small molecules
Pelabresib - Phase 3. A small molecule BET inhibitor being investigated for the treatment of myelofibrosis.
Research project: 1
Preclinical: 5
Phase 1: 3
Phase 2: 10
Phase 3: 6
Constellation Pharmaceuticals AcquisitionMorphoSys acquired Constellation Pharmaceuticals for $1.7bn cash in 2021, supported by royalty financing firm Royalty Pharma, see below. Key acquired assets include pelabresib and CPI-0209, a second-generation EZH2 inhibitor. This deal bolsters MorphoSys' position in hematological maligancies, and facilitates expansion into solid tumours.The deal was enabled by a long-term strategic funding partnership with Royalty Pharma, which provided $1.4bn up-front plus development funds and potential milestone payments. In exchange, Royalty Pharma gains rights to 100% of MorphoSys' royalties on net sales of Janssen’s plaque psoriasis antibody treatment Tremfya and 3% of future net sales of Constellation's clinical assets, including pelabresib.