On May 8, 2024 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of masked, conditionally activated biologics, reported first quarter 2024 financial results and provided a business update (Press release, CytomX Therapeutics, MAY 8, 2024, View Source [SID1234642872]).

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"CytomX’s multi-modality PROBODY therapeutic pipeline encompasses some of the most exciting areas of current oncology R&D, including T-cell engagers, ADCs, and cytokines. CytomX’s leadership and continuous innovation in the field of masked, conditionally activated biologics ideally positions us to develop novel, potent therapies for cancer patients in key areas of unmet need," said Sean McCarthy, D.Phil., chief executive officer and chairman of CytomX.

McCarthy added, "CytomX entered 2024 executing to our plan and with substantial momentum, looking towards key data readouts from our multi-modality PROBODY therapeutic pipeline over the next 12 to 24 months. Our exciting announcement today of positive initial Phase 1a clinical data for CX-904 marks the beginning of this data-rich period and we look forward to making continued progress with our broad program of masked, PROBODY T-cell engagers and to also demonstrating clinical proof of concept for CX-2051 and CX-801, for which we anticipate initial Phase 1 data in 2025."

First Quarter Business Highlights and Recent Developments

Pipeline

CX-904, PROBODY T-cell-engager (TCE) targeted to EGFRxCD3, demonstrates a favorable safety profile and encouraging anti-cancer activity in Phase 1 dose escalation. Dose escalation continues.

CX-904 is a conditionally activated PROBODY TCE designed to target the epidermal growth factor receptor (EGFR) on cancer cells and the CD3 receptor on T cells within the tumor microenvironment. CX-904 is being evaluated in an ongoing Phase 1 study.

Today, the Company announced positive initial Phase 1 dose escalation data in heavily pre-treated patients with advanced metastatic solid tumor types that are generally known to express EGFR. 19 patients were initially enrolled into non-step dosing cohorts with target doses ranging from 0.007 mg to 6 mg. 16 patients were subsequently enrolled into step-dosing cohorts with target doses ranging from 5 mg to 10 mg and with tocilizumab prophylaxis. Dose escalation continues and enrollment into a cohort with a target dose of 15 mg is ongoing.

As of the April 16, 2024 data cutoff, CX-904 demonstrated a favorable safety profile including no observed cases of CRS of any grade in step-dosing cohorts and only Grade 1 CRS observed in patients treated at the highest non-step dose. The most common treatment-related adverse events (TRAEs) were arthralgia, arthritis, rash, pruritis, and vomiting, the majority of which were low grade.
Eight patients had measurable tumor reduction, including 2 of 6 (33%) efficacy-evaluable pancreatic cancer patients with confirmed partial responses per RECIST 1.1.
Preliminary pharmacokinetic and pharmacodynamic data were consistent with the PROBODY TCE mechanism of action, including maintained masking in circulation, and CD8+ T-cell margination and tumor infiltration.
CX-904 Phase 1a dose escalation and optimization continue, with future enrollment focused on determining a recommended Phase 2 dose.
The Company expects to provide an additional Phase 1a dose escalation update by the end of 2024. These additional data will help inform next steps along with partner Amgen, towards initiation of Phase 1b expansion cohorts in specific EGFR positive tumor types.
CX-2051, an EpCAM-directed PROBODY antibody drug conjugate, first patient dosed in Phase 1 in April 2024, initial data expected in 2025.

EpCAM is a promising oncology target with significant potential that is highly expressed across many indications including colorectal, gastric, endometrial, and ovarian cancers. EpCAM has been clinically validated by locally administered, previously approved cancer therapies. To date, systemically administered anti-EpCAM therapeutics have been unsuccessful due to toxicities in certain epithelial tissues. CX-2051 utilizes a cytotoxic payload that is a derivative of camptothecin, a topoisomerase-1 inhibitor, a class of drug that has shown potent clinical anti-cancer activity in the ADC context for multiple targets and cancer types. CX-2051 has demonstrated a wide predicted therapeutic index in multiple preclinical models, constituting an opportunity for broad clinical use in large patient populations.

In April 2024, the first patient was dosed as part of the Phase 1 dose escalation of CX-2051 in patients with solid tumors generally known to express EpCAM, including CRC. The first dose cohort in the CX-2051 Phase 1 study has been cleared and dose escalation continues.
The Phase 1 dose escalation study is following a Bayesian Optimal Interval (BOIN) design and is intended to demonstrate initial clinical proof of concept to inform a potential decision to move into dose expansion cohorts in 2025.
Initial data for CX-2051 is expected in the first half of 2025.
CX-801, a dually-masked PROBODY interferon-alpha 2b, advancing to Phase 1 in Q2 2024. Executed Clinical Collaboration Agreement with Merck (known as MSD outside of the US and Canada) to evaluate CX-801 in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab).

Interferon-alpha 2b is an immunotherapeutic cytokine that has demonstrated clinical activity and gained regulatory approval previously in multiple cancer types, including locally advanced or metastatic melanoma, renal cancer and bladder cancer. IFNα2b provides a potentially superior approach to activating anti-tumor immune responses compared to other cytokines but its clinical benefit has been limited to date by severe dose-limiting toxicities. CX-801 is an optimized, dually masked, conditionally activated IFNα2b, designed to have an expanded therapeutic index that has the potential to become a cornerstone of combination therapy for a wide range of tumor types.

Announced a clinical collaboration agreement with Merck to supply KEYTRUDA for a Phase 1 study of CX-801 in combination with KEYTRUDA.
CX-801 is anticipated to initiate Phase 1 dose escalation in patients with solid tumors including melanoma, renal, and head and neck squamous cell carcinoma in Q2 2024. The Phase 1 dose escalation will utilize a BOIN design to evaluate safety and signs of clinical activity for CX-801 monotherapy and for CX-801 in combination with KEYTRUDA.
Initial Phase 1 data for CX-801 is expected in 2025.
KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

CytomX continues to make progress in its R&D partnerships.

CytomX has multiple active research and development partnerships and more than 10 ongoing research programs with major biotechnology and pharmaceutical companies (Amgen, Astellas, Bristol Myers Squibb, Moderna and Regeneron). The majority of these programs are focused on masked, conditionally activated PROBODY T-cell engagers.

In Q1 2024, CytomX achieved $10.0 million in milestones under its multi-target T-cell Engager collaboration with Astellas related to two separate PROBODY TCE programs:

A $5.0 million milestone for the initiation of GLP toxicology studies for the first clinical candidate program in the collaboration.
A $5.0 million milestone for the nomination of the second clinical candidate in the collaboration.
2024 Priorities and Key Milestones:

CX-904 (EGFRxCD3):
CX-904 Phase 1a dose escalation and optimization continue, with future enrollment focused on determining a recommended Phase 2 dose or doses.
An additional Phase 1a dose escalation update is expected by the end of 2024.
A potential decision, to be taken with Amgen, to initiate Phase 1b expansion cohorts in specific EGFR positive tumor types is expected by the end of 2024.
CX-2051 (EpCAM):
Continued Phase 1 dose escalation in solid tumors with known EpCAM expression.
Initial Phase 1a data is expected in the first half 2025.
CX-801 (IFNα2b):
Initiation of Phase 1 dose escalation in solid tumors including melanoma, renal, and head and neck squamous cell carcinoma is expected by Q2 2024.
Initial Phase 1a data is expected in 2025.
Collaborations:
Continuation of T-cell engager focused drug discovery and development activities with Bristol Myers Squibb, Amgen, Astellas, and Regeneron.
Progress with Moderna on conditionally activated mRNA-based programs.
Potential additional pre-clinical and clinical milestones in 2024 and beyond.
Q1 2024 Financial Results

Cash, cash equivalents and investments totaled $150.3 million as of March 31, 2024, compared to $174.5 million as of December 31, 2023. The cash balance as of March 31, 2024, does not include the $10.0 million of Astellas milestone achievements earned in the first quarter of 2024.

Total revenue was $41.5 million for the three months ended March 31, 2024 compared to $23.5 million for the corresponding period in 2023. The increase in revenue was driven primarily by a higher percentage of work completion of existing targets under the BMS, Moderna and Regeneron agreements as well as the $10.0 million of milestones earned under the collaboration with Astellas.

Research and development expenses increased by $0.9 million for the three months ended March 31, 2024 to $22.1 million, compared to $21.2 million for the corresponding period of 2023. This was primarily due to increased laboratory contract services and manufacturing activities related to CX-904, CX-2051 and other wholly owned and partnered programs, as well as consulting, personnel and license related expenses, offset by decreased manufacturing activities for CX-801 program and winding down of clinical study activities related to the CX-2009 and CX-2029 programs.

General and administrative expenses decreased by $0.2 million for the three months ended March 31, 2024 to $7.8 million compared to $8.0 million for the corresponding period of 2023, primarily due to lower building rent as a result of partial sublease of the Company’s headquarters.