What biotech holds in store

Green Day once sang, ‘Wake Me Up When September Ends,’ but September isn’t a month to sleep through. It is Blood Cancer Awareness Month, and while it might not be the type of cancer that receives the most attention during the year, biotech is making progress, and companies are advancing very promising solutions. 

Hematologic malignancies pose unique therapeutic hurdles. Unlike solid tumors, blood cancers are systemic; surgery or localized radiotherapy can’t contain them, and malignant cells often originate from hard-to-eradicate stem cells. This increases the risk of relapse due to minimal residual disease (MRD), where even trace cancer cells persist below detectable levels and eventually drive recurrence. CAR‑T and other cell therapies bring hope, but they face limitations too: antigen escape, immunosuppressive microenvironments, manufacturing complexity, high costs, and potentially severe side effects such as cytokine release syndrome. 

So, let’s delve into what biotech holds in store for blood cancers.  

Tackling genetic drivers of blood cancer 

One of the hallmarks of blood cancers is that many are powered by precise genetic alterations. In acute myeloid leukemia (AML), for example, chromosomal rearrangements or recurrent mutations can hijack developmental programs that normally control how blood cells mature. These genetic lesions don’t just cause cells to proliferate uncontrollably; they also lock them in an immature, stem-like state that is notoriously resistant to therapy. This is one reason why relapse remains so common in AML: even when chemotherapy or newer drugs clear most of the disease, a handful of stem-like leukemia cells can survive and reignite the cancer. 

Targeting these genetic programs directly has long been a goal in hematology. Instead of indiscriminately killing dividing cells, the idea is to switch off the transcriptional circuit that leukemia depends on. Two approaches are now leading the way: menin inhibition, which disrupts a critical protein-protein interaction in leukemias with KMT2A rearrangements or NPM1 mutations, and LSD1 inhibition, which aims to release a differentiation block by targeting an epigenetic enzyme. 

Syndax Pharmaceuticals has already shown that this concept can translate into practice. Its menin inhibitor, revumenib (Revuforj), became the first drug of its class to win FDA approval in November 2024 for relapsed or refractory acute leukemias with a KMT2A rearrangement. In June, the company announced that a supplemental filing is now under FDA priority review to extend revumenib’s use to NPM1-mutant AML, which represents a larger patient group. Several combination studies are also underway to see whether menin inhibition can deepen responses when paired with chemotherapy or venetoclax. 

A more experimental route is being pursued by Oryzon Genomics with its candidate iadademstat, a selective inhibitor of LSD1 (also known as KDM1A). LSD1 helps maintain the epigenetic state that keeps AML blasts in an undifferentiated state. By blocking it, iadademstat encourages malignant cells to resume maturation, a concept similar to differentiation therapy in acute promyelocytic leukemia but applicable to broader AML subtypes.  

In the phase 2a trial, combining iadademstat with azacitidine in newly diagnosed elderly or unfit AML patients, the overall response rate exceeded 80% with over half of patients achieving partial or complete remission. While the trial was small, these results have spurred further studies testing iadademstat in combinations with venetoclax and in genetically defined subgroups such as FLT3-mutant AML. 

Beyond inhibitors: The rise of protein degraders 

For decades, many of the proteins that drive blood cancers were considered out of reach for drug developers. Some, like transcription factors, don’t have the neat pockets that inhibitors can block. Others, like Bruton’s Tyrosine Kinase (BTK), are druggable but develop resistance mutations that blunt the effect of even the most sophisticated next-generation inhibitors. The result has been a cycle of short-lived responses followed by relapse. 

This is where targeted protein degradation comes in. Instead of trying to block a single site on a protein, degraders work by tagging the entire protein for destruction by the cell’s own disposal system. In practice, that means the cancer-driving protein is not just inhibited but removed altogether, and it doesn’t come back until the cell makes new copies. By eliminating the protein, degraders can overcome resistance mutations and open the door to targets long thought undruggable. 

It’s still early, but the first clinical programs are already showing why this approach could matter in blood cancers. Biotechs such as Nurix and Kymera are leading the charge, with degrader candidates that go after BTK, STAT3, and IRAK4; three very different but equally challenging nodes in leukemia and lymphoma. 

Nurix Therapeutics is the company most advanced in applying protein degradation to B-cell malignancies. Its lead degrader, NX-5948, is being tested in a phase 1 trial across relapsed or refractory B-cell cancers. Unlike conventional BTK inhibitors, NX-5948 removes BTK entirely, including mutant forms that resist inhibition. What sets it apart is its ability to cross the blood-brain barrier, making it relevant for patients with central nervous system involvement. Early trial readouts in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) have shown responses in heavily pretreated patients, and Nurix is preparing for late-stage development in 2025. 

Alongside NX-5948, the company is also advancing NX-2127, a dual degrader that takes down both BTK and the transcription factors IKZF1 and IKZF3. In early clinical testing, NX-2127 produced durable responses even in patients who had failed both covalent and non-covalent BTK inhibitors, a group with few remaining options. Development was briefly paused in 2024 due to a manufacturing issue, but it resumed after regulators lifted a clinical hold.  

Kymera Therapeutics has taken aim at proteins long deemed impossible to drug. Its STAT3 degrader KT-333 is the first of its kind in the clinic, designed for T-cell lymphomas and other STAT3-driven cancers. Interim phase 1 results showed up to 95% degradation of STAT3 in patient cells, evidence of pathway modulation in tumor biopsies, and early clinical responses in cutaneous T-cell lymphoma and related malignancies. With Fast Track designation in cutaneous T-cell lymphoma (CTCL) and Peripheral T-cell lymphoma (PTCL), KT-333 is shaping up as a proof-of-concept that transcription factors can be brought under therapeutic control through degradation. 

Immune engagement reimagined 

For all the progress in hematology, many patients still relapse because the immune system either can’t see the cancer or is held back by powerful brakes in the tumor microenvironment. Most of the recent breakthroughs in myeloma immunotherapy have targeted B-cell maturation antigen (BCMA), a plasma cell antigen that underpins today’s CAR-Ts, bispecifics, and, until recently, ADCs. While these treatments represent considerable progress, patients eventually relapse. 

The new wave of immune-engaging drugs tries to fix that from different angles: some re-target T cells to fresh antigens after BCMA therapy has failed; others strip away suppressive regulatory T cells (Tregs) that shield malignant T cells; and some enlist innate cells (natural killer cells) to hit leukemias that have dodged T-cell–based approaches. The common thread is precision, redirecting or modulating immunity in ways that fit the biology of blood cancers rather than fighting it. 

Domain Therapeutics is approaching blood cancer from an immunoregulatory angle. One of the barriers to effective immune responses in cancer is the presence of Tregs, which suppress anti-tumor immunity. Within tumors, a specific receptor called CCR8 is highly expressed on these Tregs, making it a promising way to selectively remove them while sparing normal immune cells elsewhere in the body. 

What makes CCR8 particularly interesting for hematology is that it isn’t just a Treg marker: in CTCL, the malignant T cells themselves can also carry CCR8. That means a therapy aimed at this receptor could hit two birds with one stone, lifting immune suppression while directly targeting the cancer cells. 

Domain’s antibody, DT-7012, is the first of its kind to enter the clinic for blood cancer. Preclinical data have shown strong selectivity for CCR8, and the company started phase 1/2 studies in solid tumors in June 2025, and a trial in CTCL is also expected. 

Where Treg depletion aims to lift the brakes, Roche and Genentech’s cevostamab tries to press the gas pedal by redirecting T cells to a new target in myeloma. Cevostamab is a bispecific antibody that binds FcRH5 on myeloma cells and CD3 on T cells, enabling T-cell killing even after prior BCMA-directed therapies have failed. Initial phase 1 results presented at EHA 2024 and updated at ASH 2024, reported encouraging responses in post-BCMA cohorts.  

Affimed is pushing on a third front: mobilizing the innate immune system. Its candidate AFM28 works by binding to CD123, a protein found on AML blasts, while at the same time engaging natural killer (NK) cells through their CD16A receptor. This brings NK cells into close contact with leukemia cells and prompts them to destroy the cancer. 

Early results from the ongoing phase 1 trial have shown the first signs of clinical activity in relapsed or refractory AML, including 40% of patients achieving remission. The safety profile so far appears manageable, and Affimed is already positioning AFM28 for combinations with allogeneic NK cell therapies. If these results hold up, AFM28 may provide a chemo-free option in a setting where T-cell–based approaches have had limited success. 

Next-gen cell therapies in blood cancer 

CAR-T changed the game in blood cancers, but it still comes with practical hurdles: collecting a sick patient’s own T cells, manufacturing the product, and waiting weeks to treat a disease that often won’t slow down. The new wave of cell therapies tries to fix that in two ways: make cells available off-the-shelf so treatment can start quickly and engineer them to be gentler and more scalable without losing punch. That’s where allogeneic (donor-derived) CAR-T and iPSC-derived NK cells come in. 

CRISPR Therapeutics’ CTX112 is a next-generation, allogeneic CD19 CAR-T engineered with multiple CRISPR edits to improve expansion and persistence while evading host immunity. Because it starts from healthy donor T cells, CTX112 is designed to be ready when the patient is, rather than made from scratch each time.  

CRISPR Therapeutics is also advancing CTX130, an allogeneic CAR-T that targets CD70, a marker frequently expressed in T-cell lymphomas and some leukemias but largely absent from healthy T cells. T-cell cancers have long been challenging for CAR-T development because most potential targets are also present on normal T cells, raising the risk of wiping out the very immune cells needed for the therapy to function. Early clinical data published in The Lancet Oncology in 2025 showed that CTX130 induced objective responses in 16 out of 31 patients. Out of these 16 patients, 6 experienced a complete response and 10 a partial response. It is important to note that 21 patients died during the trial, 16 from progressive disease and five from adverse events considered unrelated to CTX130 treatment. 

If CTX112 is about speed and access, Fate Therapeutics’ FT596 is about scale and tolerability. It is the first iPSC-derived CAR-NK therapy to complete a human oncology trial, with results from a phase 1 study in B-cell lymphomas published in January 2025. Unlike autologous CAR-T, FT596 is manufactured in bulk from a single induced pluripotent stem-cell line, making it truly off-the-shelf. 

The engineered cells come with a built-in “triple toolkit”: a CAR targeting CD19, a non-cleavable CD16 receptor to work alongside anti-CD20 antibodies like rituximab, and an IL-15 fusion to support persistence. In 86 heavily pretreated lymphoma patients, FT596 proved well tolerated, with no neurotoxicity and only mild cytokine release in a few cases, while still inducing durable responses across indolent and aggressive subtypes. The trial has now established a recommended phase 2 dose, setting the stage for broader testing.  

Other blood cancer candidates to keep an eye on

Beyond the areas we’ve covered, a few first-in-class or differentiated programs are moving fast enough to deserve a mention.  

Geron’s imetelstat (RYTELO): switching off telomerase 

Telomerase lets malignant progenitors keep dividing by repairing chromosome ends; shutting it down aims at the “stemness” that drives chronic relapse. In June 2024, imetelstat became the first telomerase inhibitor ever approved for transfusion-dependent lower-risk myelodysplastic syndrome (MDS). The next hurdle is proving a survival benefit in relapsed or refractory myelofibrosis, a blood cancer marked by scarring of the bone marrow, and a risk of progression to acute leukemia. The ongoing phase 3 trial is designed with overall survival as its primary endpoint, and results are expected to show whether imetelstat can extend life in a setting where options are scarce.  

AbbVie’s pivekimab sunirine (PVEK): a CD123 ADC for BPDCN 

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare but highly aggressive blood cancer, often first appearing with skin lesions before spreading to the marrow and lymph nodes. Most BPDCN cells express CD123, which makes this receptor the primary therapeutic target in the disease. The only approved CD123-directed therapy so far, tagraxofusp, brought the first real progress but comes with safety limitations.  

AbbVie’s pivekimab sunirine (PVEK) takes a different route, coupling an anti-CD123 antibody to a DNA-alkylating payload. In newly diagnosed BPDCN, phase 1/2 data presented in 2025 showed an overall response rate of 85%, with 70% complete remissions and a safety profile that looked more manageable. 

Autolus’ AUTO4: TRBC1-selective CAR-T for T-cell lymphomas 

CAR-T in T-cell cancers risks wiping out healthy T cells along with the tumor. AUTO4 exploits a quirk of T-cell biology: tumors express either TRBC1 or TRBC2, but not both. By targeting TRBC1, AUTO4 spares the TRBC2 compartment, preserving immune function. In a phase 1 trial published in Nature Medicine in January 2025, AUTO4 produced durable complete metabolic remissions with a manageable safety profile. The results provide the first solid evidence that constant-region targeting can make CAR-T a viable option in peripheral T-cell lymphoma. 

Blood cancer, from promise to practice 

The market for blood cancer therapies is projected to double over the next decade, reaching more than $160 billion by 2034. That growth reflects both the rising burden of these diseases but also the investors’ interest in companies working in the area. As the field moves forward, the test will be whether these first-in-class approaches, whether degraders, new immune engagers, or next-generation cell therapies, can deliver durable benefit and make their way into everyday practice. 

While it’s hard to pin down an exact number, estimates suggest there are several hundred novel cancer agents in preclinical development. Yet history tells us that fewer than ten of these typically make it into clinical trials, and only one or two ultimately reach approval. This doesn’t mean that the future blood cancer blockbuster treatment isn’t in preclinical development today, more that it is still early to say.