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We are a biopharmaceutical company focused on the development of targeted
oncology therapies. We believe that the pursuit of novel or underexplored targets will be central to the next generation of transformative
therapies. For that reason, we pursue therapeutics that we believe have best-in-class or first-in-class potential. Our goal is to establish
a broad pipeline of preclinical and clinical assets which we can efficiently develop to value inflection points. To support that goal,
we pair business development activity with significant investment in our internal discovery programs.
Our pipeline is centered on three preclinical assets: IM-1021, a ROR1
ADC; IM-4320, an anti-IL-38 immunotherapy candidate; and a currently undisclosed candidate that is a FAP radioligand therapy, or RLT,
candidate. We anticipate submitting investigational new drug applications, or INDs, for each of these programs in the first quarter of
2025. We are not aware of any active development programs targeting IL-38 and believe that IM-4320, if successfully developed and approved,
would be a first-in-class immunotherapy. We believe that each of these drugs has the potential to improve outcomes for patients across
multiple indications.
On February 5, 2024, we signed a definitive asset purchase agreement
to acquire AL102, an investigational gamma secretase inhibitor, or GSI, currently under evaluation in a Phase 3 trial for the treatment
of desmoid tumors. We expect the purchase of AL102 (which also includes AL101, a related asset) to close in late Q1 or early Q2 2024.
Following the closing of that deal, we will become a clinical stage company. Based on our evaluation of Phase 2 data, we believe that
AL102 has the potential, if approved, to establish a new standard of care for patients with desmoid tumors.
Immunome's business model is built upon our expertise in discovering
and developing targeted therapies as well as its ability to evaluate and acquire high-potential assets. We believe that the successful
track record of the leadership team will make the Company more attractive to companies selling assets, especially early-stage biotechnology
companies that lack resources to efficiently develop their assets.
Our perspective is that the most important considerations when acquiring
an asset are the quality of its preclinical or clinical data and the economic terms it can be acquired on. Accordingly, we are willing
to consider assets across multiple modalities, including antibody drug conjugates, or ADCs, RLTs, naked antibodies, small molecules and
more. We believe that effectively pursuing a novel target requires selecting a modality that is appropriate to the target biology.
At present, our internal discovery efforts are centered on ADCs and
RLTs. We believe that a broad toolbox of linkers and payloads is necessary to design and develop a broad pipeline of ADCs, as different
targets may require different payloads to achieve optimal efficacy and therapeutic index. The novel linker-effector unit we exclusively
licensed from Zentalis is an important component of this toolbox, and we have efforts underway to develop additional linkers and payloads.
We also believe that the incorporation of albumin binders into radioligand therapies provides a differentiated approach that can increase
the dose of radiation absorbed by patient tumors.
Immunome's Discovery Platform utilizes proprietary hybridoma
technology to immortalize memory B cells isolated from oncology patient samples. This enables the production of sufficient quantities
of antibodies to perform high-throughput functional screening, allowing for the recognition of antibodies and targets whose role in cancer
was not previously appreciated. In January 2023, we announced an agreement with AbbVie under which AbbVie paid $30 million upfront
for access to up to 10 targets identified by the Discovery Platform.
Immunome is led by Clay Siegall, PhD, President and Chief Executive
Officer. Dr. Siegall previously served as CEO of Seagen, which he co-founded in 1997 and led for nearly 25 years. During his tenure,
Seagen earned FDA approvals for four cancer therapies. Pfizer purchased Seagen in December 2023. Dr. Siegall joined Immunome
in connection with Immunome's acquisition of Morphimmune, a preclinical biotechnology company led by Dr. Siegall, in October 2023.
In addition to Dr. Siegall, three members of our current management
team joined Immunome from Morphimmune in October 2023. Jack Higgins, PhD, Immunome's Chief Scientific Officer, held the
same role at Morphimmune, He was previously the Chief Development Sciences Officer at Molecular Templates, where he led discovery and
development efforts for multiple clinical candidates and co-invented the company's Engineered Toxin Body platform. Bruce Turner,
MD, PhD, Immunome's Chief Strategy Officer, held the same role at Morphimmune and previously founded several biotechnology
companies including Xanadu Bio and Gennao Bio. Max Rosett, Executive Vice President, Operations, and Interim Chief Financial Officer at
Immunome, served as Acting Chief Operating Officer at Morphimmune. Mr. Rosett previously served as Principal at Research Bridge Partners,
where he led Research Bridge Partners' investment in Morphimmune's Series A financing.
Bob Lechleider, MD, serves as the Chief Medical Officer of Immunome.
Dr. Lechleider was most recently the Chief Medical Officer of OncoResponse and previously worked with Dr. Siegall at Seagen,
where he was responsible for directing the development of early and late-stage portfolios. Phil Roberts, serves as the Chief Technical
Officer of Immunome. Dr. Roberts previously served as SVP, Technical Operations at Mirati Therapeutics, where he led the CMC development
of Krazati, Mirati's first approved product. Sandra Stoneman, JD, serves as Chief Legal Officer of Immunome. She joined Immunome
from Duane Morris LLP, where she was an equity partner. Kinney Horn serves as our Chief Business Officer. He previously served in the
same role at Olema Oncology and spent more than 15 years at Genentech.
On January 8, 2024, we announced that we had entered into an exclusive,
worldwide license agreement under which we licensed from Zentalis ZPC-21 (now IM-1021), a preclinical-stage ADC targeting the receptor
tyrosine kinase like orphan receptor 1, or ROR1. ROR1 has an oncofetal expression pattern, with little or no expression in healthy tissue,
and is expressed on solid and liquid tumors. We believe ROR1 has been clinically validated as an ADC target through clinical trials of
a competitor ADC in multiple B-cell malignancies.
The expression pattern of ROR1 suggests that it may have clinical utility
as a therapeutic target in multiple solid and liquid tumor indications, including diseases with large patient populations and high unmet
need (Figure 1). However, the moderate-to-low expression and slow internalization of ROR1 present challenges to developing a successful
ADC for the treatment of ROR1-positive solid tumors. Our approach to overcoming these challenges is focused on pursuing development of
IM-1021, which incorporates an ROR1 antibody that is designed to promote internalization; uses a linker-payload combination that we believe
provides a potentially improved therapeutic index and may allow for higher clinical dosing; and contains a payload that is designed to
maximize the potential bystander effect and supports a drug-antibody ratio, or DAR, of 8.
IM-1021 incorporates a cleavable, undisclosed linker that is used to
conjugate a camptothecin derivative (a topoisomerase I inhibitor) to the ROR1 antibody via cysteine conjugation, and provides a DAR of
8. In preclinical studies, IM-1021 showed sustained tumor regression in a mouse model triple-negative breast cancer, or TNBC. In
this model, IM-1021 dosed weekly for three weeks at 2.5 mg/kg or 5.0 mg/kg demonstrated superior reductions in tumor volume compared
with the same respective dose of a competitor, vedotin payload ROR1 ADC, with no meaningful weight loss observed (Figure 2).
Figure 2. IM-1021 showed favorable activity and safety findings
in a TNBC mouse model
We expect to submit an IND for the IM-1021 program to the FDA in the
first quarter of 2025. Subject to obtaining an IND, our IM-1201 clinical strategy is designed to efficiently evaluate dose escalation
in patients with solid tumors or lymphoma, followed by potential expansion of the solid tumor clinical program into targeted indications,
potentially including non-small cell lung cancer, breast prostate, pancreatic, and gastric cancer, and expansion of the lymphoma program
into diffuse large B-cell lymphoma and mantle cell lymphoma. Concurrent with the dose escalation and expansion studies, we plan to conduct
non-clinical studies evaluating IM-1021 in combination with other therapies, particularly in B-cell malignancies, and to evaluate and
develop potential companion diagnostics that could help identify patients most likely to respond to IM-1021. Our strategy is to pursue
pivotal clinical studies in indications that have shown compelling clinical outcomes in earlier-stage trials, present significant commercial
opportunities, have the potential for enhanced outcomes using a companion diagnostic, and offer potential for accelerated approval.
177Lu-FAP Radioligand Therapy
Through our merger with Morphimmune, we acquired a FAP-targeted Lu-177
radiotherapy development candidate for the treatment of solid tumors. FAP, or fibroblast activation protein, serves as a tumor-specific
marker due to its broad expression on cancer associated fibroblasts. Cancer-associated fibroblasts are the most common tumor stromal cell,
with expression in 75% of solid tumors. Our FAP-Lu RLT candidate is designed to deliver radioactive 177Lu directly to FAP-expressing
cells, where the "bystander" effect of the radiation may target nearby tumor cells. We believe this RLT approach could overcome
the limitations, such as poor internalization and low expression on tumor cells, that make FAP an unsuitable target for ADCs.
Our FAP-targeted radiotherapy candidate has four functional domains:
We have conducted preclinical studies demonstrating that incorporating
albumin binders into RLTs improved biodistribution and in vivo pharmacokinetic profiles. Strong albumin binding resulted in higher total
absorbed doses in tumor compared with liver and kidney (Figure 4) and also led to increased and prolonged FAP-RLT levels in serum when
administered intravenously (Figure 5).
We are evaluating a series of potential drug
candidates that explore options for each of the four domains in order to select the combination that we believe may be most likely to
deliver therapeutic benefits in cancer patients. Several candidates have shown substantial tumor regression in an animal model of
glioblastoma (Figure 6A), with no weight loss observed (Figure 6B).
We believe our growing body of preclinical
data for these candidates demonstrates desirable characteristics that support the further development of a FAP RLT. These preclinical