The pipelines cover ADC and RLT. This innovative pharmaceutical company has raised nearly $600 million in total financing.

In January 2025, Immunome completed a $150 million financing round. This round of financing will drive the clinical translation of the core pipeline. In March, Immunome announced that the first patient was dosed in the Phase I clinical trial of IM - 1021, an ADC (antibody - drug conjugate) targeting ROR1. The enrollment of the Phase III RINGSIDE trial for its core product pipeline, Varegacestat (AL102), has also been completed, and the topline data is expected to be announced in the second half of 2025.

Immunome's core competitiveness lies in its rapid antibody screening and precise delivery technologies. The treatment advantages of high efficiency, precision, and high safety have broken through the industry bottlenecks of "off - target damage" and long R & D cycles in traditional cancer treatments.

This clinical - stage targeted oncology company has raised a total of $598.9 million in 21 rounds of financing. After 17 years since its establishment, what makes Immunome worthy of continuous investment from investors?

Utilizing natural antibodies to solve the precision problem of off - target damage

The limitations of traditional chemotherapy and radiotherapy lie in the lack of specificity in their mechanisms of action. While attacking cancer cells, drugs or radiation will damage healthy cells that divide rapidly (such as bone marrow and digestive tract cells) without discrimination, leading to serious side effects such as decreased immunity and hair loss in patients. This kind of attack causes up to 60% damage to healthy human tissues. Taking pancreatic cancer as an example, although traditional radiotherapy can shrink tumors, patients are prone to serious complications such as digestive tract ulcers.

According to data from the Tufts Center for the Study of Drug Development, it takes an average of 10 years and costs about $2.6 billion to develop a new drug, and more than 90% of candidate drugs fail in clinical performance due to off - target or toxicity issues. Traditional antibody screening requires searching for a "needle in a haystack" from tens of thousands of compounds, and the R & D of oncology drugs generally faces challenges of long cycles and high costs.

Immunome's advantage lies in its unique R & D pipeline strategy for ADCs. It targets the unmet needs of solid tumors and hematological malignancies through a novel topoisomerase inhibitor payload, HC74, and the selection of differentiated targets. At the same time, Immunome's pipeline layout is both balanced and forward - looking. By combining ADC and RLT (radioactive ligand therapy), it reduces the risk of target failure and improves commercial benefits.

Before understanding the core pipeline, we first need to clarify its core technologies, including the two technological cornerstones from antibody screening to precise delivery: the MemoryB platform and the Targeted Effector platform.

● Memory B cell technology: An antibody discovery platform that "leverages" from patients' bodies

The MemoryB cell hybridoma technology platform goes through three processes: sample extraction, cell fusion, and antibody screening. First, the platform isolates memory B cells from patients' blood or tumor tissues. These cells naturally carry information about anti - tumor antibodies because they have been exposed to tumor antigens. Then, the memory B cells are fused with myeloma cells to form hybridoma cells, which have the ability to proliferate indefinitely. Finally, through high - throughput screening technology, highly effective antibodies against specific tumor antigens are screened from the hybridoma cells.

Compared with traditional therapies, this breakthrough has improved the affinity and specificity of antibodies.

For patients with drug resistance, the effectiveness of drug delivery gradually weakens. Drug - resistant tumors often produce neoantigens through gene mutations or epigenetic changes, and these antigens are difficult to target in traditional therapies. Immunome's MemoryB cell hybridoma technology directly extracts memory B cells from patients' bodies, and these cells naturally carry information about antibodies against tumor - specific antigens. Therefore, it is particularly suitable for drug - resistant tumors and rare targets.

● Targeted Effector: A "guidance system" that increases radiotherapy dose by 5 times

Immunome's Targeted Effector platform solves the core contradiction in tumor treatment through modular design - how to maximize drug lethality while avoiding off - target damage. The platform can adapt the optimal effector molecules and delivery strategies according to the characteristics of different targets.

For targets that require strong cell killing, the platform can deploy toxin payloads such as the topoisomerase inhibitor HC74 and achieve the drug - to - antibody ratio through site - specific cysteine conjugation technology while maintaining stability. For complex scenarios such as the solid tumor microenvironment, it switches to the radionuclide strategy, using the iodophenyl albumin - binding domain to extend the drug circulation time and significantly increase the exposure of tumor tissues.

Traditional ADCs are difficult to develop into drugs due to low internalization efficiency of targets. However, the Targeted Effector covers surrounding cells through the radiation bystander effect, transforming the originally undruggable stromal target FAP into an effective target.

Secondly, there is the linker technology. Protease - cleavable linkers ensure that toxins are only released inside tumor cells, while pH - sensitive linkers are activated in the slightly acidic tumor microenvironment. For example, the protease - sensitive linker of IM - 1021 only releases toxins inside tumor cells, reducing off - target toxicity. These characteristics are the key reasons why a single dose of IM - 3050 can achieve tumor regression in glioma models.

In terms of R & D efficiency, after the team completes the screening of antibodies for a new target, it can directly deploy the verified effector modules for assembly. The development of the pipeline from the FAP ligand to IM - 3050 only took 11 weeks, while the average development time for traditional radiopharmaceuticals is 9 months.

In addition to the improvement in R & D efficiency, the platform achieves precise treatment through the "ligand - effector molecule" complex. It uses small molecule ligands to achieve antibody - level targeting, precisely delivering radioactive isotopes or cytotoxins, increasing the tumor radiation dose of 177Lu - FAP by 5 times compared with traditional radiotherapy while reducing damage to healthy tissues.

The platform also has strong expandability. After the verification of a single target (such as FAP - RLT), it can quickly switch to similar targets. Secondly, the platform advantage of parallel ADC + RLT paths allows the platform technology to quickly shift to other directions even when a certain type of target fails in clinical trials.

ADC leading the way, multi - target pipeline for coordinated development

Currently, three product pipelines of Immunome have entered the clinical stage. The core pipeline project is Varegacestat (formerly AL102), a γ - secretase inhibitor. The other two are IM - 1021 (ROR1 ADC) and IM - 3050 (RLT).

● Varegacestat (AL102): An oral targeted drug for rare sarcomas

Desmoid tumors are a rare type of sarcoma. Approximately 5,500 - 7,500 patients in the United States face the dilemma of having no effective systemic treatment. Immunome's AL102 (Varegacestat) is an oral γ - secretase inhibitor that inhibits tumor growth by blocking the NOTCH pathway. The core of its mechanism lies in inhibiting the cleavage of the Notch receptor by γ - secretase, preventing the release and nuclear translocation of the oncogenic Notch intracellular domain (NICD), and thus truncating the activation of downstream pro - survival genes (such as HES1 and MYC).

For desmoid tumors that are difficult to radically cure by surgery and ineffective with chemotherapy, the Phase II trial showed that the objective response rate (ORR) in the 1.2 mg daily dose group reached 64%, significantly better than the historical control (chemotherapy ORR < 10%). In addition, by optimizing the subtype selectivity of γ - secretase, the risk of ovarian dysfunction was reduced to 55.6% (75% for the similar drug nirogacestat), avoiding the common gastrointestinal toxicity of traditional Notch inhibitors.

● IM - 1021 (ROR1 ADC): Double drug loading to overcome drug resistance in solid tumors

The drug resistance of solid tumors is essentially a process in which tumor cells evade drug killing through multiple mechanisms driven by genomic instability. Targeting ROR1 (receptor tyrosine kinase), which is highly expressed in cancers such as non - small cell lung cancer (NSCLC) and triple - negative breast cancer (TNBC), Immunome developed IM - 1021 (an ADC targeting ROR1).

This drug uses a DAR8 design (by stably connecting 8 toxins to the antibody, achieving a balance between "high drug loading" and "stability", with a drug loading twice that of traditional ADCs). It is loaded with the TOP1 inhibitor HC74 payload and has both a bystander effect and optimized antibody affinity.

The first patient was dosed in the Phase I trial of this drug in the first quarter of 2025, with a starting dose of 2 mg/kg. Preclinical data showed that it can achieve complete remission (CR) in TNBC (MDA - MB - 468) and NSCLC PDX (patient - derived xenograft models), and has better tolerance than Merck's similar drug MK - 2140. In the future, it is planned to expand to indications such as diffuse large B - cell lymphoma (DLBCL).

In addition to the clinical - stage products, IM - 1617, IM - 1335, and IM - 1340 are all preclinical ADCs targeting undisclosed targets expressed in various solid tumors.

● IM - 1617: A bifunctional ADC that activates the immune response of "cold tumors"

IM - 1617 is designed for "cold tumors" where traditional immunotherapies fail. Cold tumors refer to tumor types where immune cells (especially cytotoxic T cells) cannot infiltrate or be activated. The microenvironment of such tumors lacks immune cell infiltration and is filled with inhibitory cells (such as Treg and M2 macrophages) and inhibitory factors (such as TGF - β and IL - 38).

Traditional immunotherapies fail because drugs such as PD - 1 antibodies need pre - existing T cells to be effective, but in cold tumors, T cells either cannot enter or will be interfered with by immune inhibitory factors if they do enter.

The cleverness of IM - 1617 lies in its innovative integration of a TLR7/8 agonist payload. This ADC targets the tumor - specific antigen CLDN18.2 and precisely delivers immune - stimulating factors to the lesions of gastric and pancreatic cancers, breaking the immunosuppressive microenvironment. Preclinical data showed that while inducing apoptosis of tumor cells, the drug activates tumor - infiltrating T cells and dendritic cells, transforming "cold tumors" into "hot tumors" sensitive to PD - 1 inhibitors.

● IM - 1335: DLL3 that solves the drug resistance problem in small cell lung cancer

Aiming at the dilemma of rapid recurrence after treatment in small cell lung cancer patients, IM - 1335 uses a bispecific antibody to target the membrane - proximal domain of DLL3 (a cell surface protein specifically expressed in various malignancies, especially playing a key role in neuroendocrine tumors). This design effectively blocks the feedback activation of the Notch signal - this mechanism is the key factor leading to drug resistance in chemotherapy and Tarlatamab. The novel topoisomerase inhibitor HC74 it carries has been modified for brain enrichment, with its ability to penetrate the blood - brain barrier increased by 5 times, showing strong clearance ability for brain metastases. In the circulating tumor cell model, a single dose can clear 99% of DLL3 - positive tumor stem cells.

● IM - 1340: An intelligent antibody drug that overcomes the HER2 resistance spectrum

To address the problem of secondary drug resistance in HER2 - positive breast cancer, IM - 1340 breaks through the limitations of traditional ADCs through a triple mechanism. Its antibody can simultaneously bind to domains II and IV of the HER2 receptor, effectively blocking the formation of HER2 - HER3 heterodimers that cannot be inhibited by trastuzumab. The linker is designed to be sensitive to the pH of the tumor microenvironment, releasing the potent payload AS269 only in acidic tumor tissues.

The innovative "bystander effect enhancer" promotes the diffusion of the drug to cells with low HER2 expression. In a model carrying dual HER2 L755S/T798I drug - resistant mutations, IM - 1340 led to the gradual regression of tumors without recurrence within 6 months. This broad - spectrum coverage ability for drug - resistant mutation spectra brings new hope for long - term survival to patients with advanced breast cancer.

RLT assistance to overcome the barrier problem of the tumor microenvironment

In addition to ADC drugs, RLT (radioactive ligand therapy) is also an important R & D direction promoted by Immunome. Its core pipeline is IM - 3050.

In the treatment of solid tumors, the barrier of the tumor microenvironment is a major core problem. This barrier is composed of cancer - associated fibroblasts (CAFs), immunosuppressive factors, and tumor cell heterogeneity, and traditional drugs often have difficulty breaking through it. The response rate of common chemotherapy drugs in solid tumors is often less than 20%, and antibody drugs also have difficulty penetrating the stromal layer due to their large molecular weight. Immunome's RLT therapy precisely destroys this barrier through three steps: precise targeting - long - lasting circulation - radiation synergy.

Taking IM - 3050 as an example, it overcomes the defect of low internalization rate of traditional ADCs targeting FAP by combining the 177 - Lu isotope with the albumin - binding domain.

First, there is precise targeting. They targeted the FAP protein, which is highly specifically expressed on the surface of cancer - associated fibroblasts (CAFs) (this target is significantly enriched in 75% of solid tumors). The lead compound IM - 3050 developed by the team shows strong binding force (Kd < 1 pM), and this binding makes the drug precisely adsorb on the core builders of the tumor microenvironment like a magnet.

Then, there is the problem of long - lasting drug circulation. Through the original iodophenyl albumin - binding domain modification technology, the researchers successfully increased the plasma exposure (AUC) of the drug to 20 times that of competitors (70,531 vs. 3,862 h•ng/mL) and extended the half - life to 6 hours. This modification allows more active ingredients to break through the barrier and continuously accumulate in tumor tissues.

Finally, there is the radiation synergy mechanism. The 177Lu nuclide it carries continuously releases high - energy β - rays. While precisely clearing FAP - positive CAFs cells, it forms a strong "bystander effect" with a 2 mm radiation radius, which can simultaneously destroy surrounding tumor cells and disrupt the microenvironment ecosystem on which tumors depend for survival.

In the first quarter of 2025, Immunome submitted an IND (Investigational New Drug application) for IM - 3050 and plans to start a Phase I trial in the second half of the year. Preclinical studies showed that a single - dose treatment can lead to tumor regression in the U87MG glioma model, and no serious adverse reactions were observed, indicating good safety.

An experienced ADC veteran at the helm, about to make a "thrilling leap" from the laboratory to the market

Immunome's competitiveness also stems from its composite talent team. In 2024, the joining of Dr. Clay Siegall, the new CEO, marked a strategic transformation for Immunome. The plan is to push at least two pipelines into Phase II clinical trials before 2026 and expand global market coverage through technology licensing partnerships. He has led the commercialization