CytomX Therapeutics Inc

Previous wording

We are a clinical-stage, oncology-focused biopharmaceutical company focused on developing novel, conditionally activated, masked biologics designed to be preferentially unmasked and activated in the tumor microenvironment. We aim to build a commercial enterprise to maximize our impact on the treatment of cancer. By pioneering a novel class of localized biologic drug candidates, powered by our PROBODY® therapeutic technology platform, we lead the field of masked, conditionally activated oncology therapeutics and have established biologics localization as a strategic area of research and development. Our vision is to transform lives with safer, more effective therapies with the goal to address major unmet needs in oncology.

Current wording

We are a clinical-stage, oncology-focused biopharmaceutical company focused on developing novel, conditionally activated, masked biologics designed to be preferentially unmasked and activated in the tumor microenvironment. We aim to build a commercial enterprise to maximize our impact on the treatment of cancer. By pioneering a novel class of localized biologic drug candidates, powered by our PROBODY® therapeutic technology platform, we lead the field of masked, conditionally activated oncology therapeutics and have established biologics localization as a strategic area of research and development in the biopharmaceutical industry. Our vision is to transform lives with safer, more effective therapies with the goal to address major unmet needs in oncology.

Previous wording

On May 8, 2024, we reported a Phase 1a data update based on an April 16, 2024 data cutoff. As of the data cutoff, the CX-904-101 study had enrolled 35 patients with advanced metastatic solid tumor types that are generally known to express EGFR, including pancreatic, colorectal (CRC), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), gastric, and esophageal cancers. Patients enrolled in the study were heavily pre-treated and had a median of 4 prior lines of therapy. 19 patients were enrolled into initial non-step dosing cohorts with target doses ranging from 0.007 mg to 6 mg, and 16 patients were subsequently enrolled into step-dosing cohorts with target doses ranging from 5 mg to 10 mg and with tocilizumab prophylaxis. Enrollment into a cohort with a target dose of 15 mg is ongoing.

Current wording

On May 8, 2024, we reported initial Phase 1a data based on an April 16, 2024 data cutoff. As of the data cutoff, the CX-904-101 study had enrolled 35 patients with advanced metastatic solid tumor types that are generally known to express EGFR, including pancreatic, colorectal (CRC), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), gastric, and esophageal cancers. Patients enrolled in the study were heavily pre-treated and had a median of 4 prior lines of therapy. 19 patients were enrolled into initial non-step dosing cohorts with target doses ranging from 0.007 mg to 6 mg, and 16 patients were subsequently enrolled into step-dosing cohorts with target doses ranging from 5 mg to 10 mg and with tocilizumab prophylaxis. As of the April 16, 2024 data cutoff enrollment into a cohort with a target dose of 15 mg was ongoing.

Previous wording

As of the cutoff date, CX-904 demonstrated a favorable safety profile that supports administration and monitoring of enrolled patients in an outpatient setting.1 There were no observed cases of cytokine release syndrome (CRS) of any grade in step-dosing cohorts as of the cutoff date. In non-step dosing cohorts, only Grade 1 CRS was observed in patients treated at the highest dose of 6 mg. Overall, the most common treatment-related adverse events (TRAEs) were rash, arthralgia, arthritis, pruritis, and vomiting, the majority of which were low grade, being observed in 14 (40%), 13 (37%), 5 (14%), 5 (14%) and 5 (14%) of patients, respectively. Grade 3 adverse events were tenosynovitis (n=1), arthralgia (n=2), arthritis (n=1), rash (n=1).

Current wording

As of the cutoff date, CX-904 demonstrated a favorable safety profile. There were no observed cases of cytokine release syndrome (CRS) of any grade in step-dosing cohorts as of the cutoff date. In non-step dosing cohorts, only Grade 1 CRS was observed in patients treated at the highest dose of 6 mg. Overall, the most common treatment-related adverse events (TRAEs) were rash, arthralgia, arthritis, pruritis, and vomiting, the majority of which were low grade, being observed in 14 (40%), 13 (37%), 5 (14%), 5 (14%) and 5 (14%) of patients, respectively. Grade 3 adverse events were tenosynovitis (n=1), arthralgia (n=2), arthritis (n=1), rash (n=1).

Previous wording

As of the April 16, 2024 data cutoff, 8 patients had measurable tumor reduction per RECIST 1.1, including 2 of 6 efficacy-evaluable patients (33%) with pancreatic cancer with confirmed partial responses. All 6 efficacy-evaluable patients with pancreatic cancer achieved disease control (objective response or stable disease). For the two patients with a confirmed partial response, one patient (6 mg target dose) achieved an 83% tumor reduction. A second patient (5 mg target dose) with a confirmed response achieved a 51% tumor reduction and remained on study treatment as of the data cutoff. In addition, a third pancreatic cancer patient maintained stable disease with no evidence of tumor growth through 3.5 months of study treatment, remaining on treatment as of the data cutoff.

Current wording

As of the April 16, 2024 data cutoff, 8 patients had measurable tumor reduction per RECIST 1.1, including 2 of 6 efficacy-evaluable patients (33%) with pancreatic cancer with confirmed partial responses. All 6 efficacy-evaluable patients with pancreatic cancer achieved disease control (objective response or stable disease). For the two patients with a confirmed partial response, one patient (6 mg target dose) achieved an 83% tumor reduction. A second patient (5 mg target dose) with a confirmed response achieved a 51% tumor reduction and remained on study treatment as of the data cutoff. In addition, a third pancreatic cancer patient maintained stable disease with no evidence of tumor growth through 3.5 months of study treatment, and remained on treatment as of the data cutoff.

Previous wording

Our pipeline also includes CX-2051, a wholly-owned conditionally activated, PROBODY ADC paired with a next-generation camptothecin payload and directed toward the epithelial cellular adhesion molecule (EpCAM). CX-2051 is licensed from ImmunoGen. CX-2051 has been tailored to optimize the therapeutic index for the systemic treatment of EpCAM-expressing epithelial cancers where previous industry efforts targeting EpCAM have not been successful due to dose-limiting toxicities. CX-2051 has demonstrated a wide predicted therapeutic index and strong preclinical activity and tolerability in multiple preclinical models, including colorectal cancer.

Current wording

Our pipeline also includes CX-2051, a wholly-owned conditionally activated, PROBODY ADC paired with a next-generation camptothecin payload (Topoisomerase-1 inhibitor) and directed toward the epithelial cellular adhesion molecule (EpCAM). CX-2051 is licensed from AbbVie (formerly ImmunoGen). CX-2051 has been tailored to optimize the therapeutic index for the systemic treatment of EpCAM-expressing epithelial cancers where previous industry efforts targeting EpCAM have not been successful due to dose-limiting toxicities. CX-2051 has demonstrated a wide predicted therapeutic index and strong preclinical activity and tolerability in multiple preclinical models, including colorectal cancer.

Previous wording

The IND for CX-2051 was cleared by the FDA in January 2024 and Phase 1 clinical initiation in EpCAM expressing solid tumors, including CRC commenced in April 2024. The Phase 1 dose escalation will follow a Bayesian Optimal Interval (BOIN) design and is intended to demonstrate clinical proof of concept to potentially move into dose expansion studies in 2025.

Current wording

The IND for CX-2051 was cleared by the FDA in January 2024 and Phase 1 clinical initiation in EpCAM expressing solid tumors, including CRC commenced in April 2024. As of August 2024, the third cohort in the Phase 1 study had been opened with early enrollment focused primarily in CRC. The Phase 1 dose escalation is intended to demonstrate clinical proof of concept to potentially move into dose expansion studies in 2025. Initial Phase 1 data for CX-2051 is expected in the first half of 2025.

Previous wording

Another wholly-owned product candidate is CX-801, an interferon ("IFN") alpha-2b PROBODY. IFNα2b provides a potentially superior approach to activating anti-tumor immune responses than other cytokines. CX-801 is a dually masked, conditionally activated version of IFNα2b that has the potential to become a cornerstone of combination therapy for a wide range of tumor types. The IND for CX-801 was cleared by the FDA in January 2024 and initiation of Phase 1 dose escalation in solid tumors including melanoma, renal, and head and neck squamous cell carcinoma is expected in the first half of 2024. In Phase 1 dose escalation, we will use a BOIN design to evaluate safety and signs of clinical activity for CX-801 and progress into combinations, where CX-801 has the potential to be cornerstone of therapy, including in combination with checkpoint inhibitors. On May 7, 2024 CytomX announced a clinical collaboration with Merck to evaluate CX-801 in combination with KEYTRUDA® in the Phase 1 study.

Current wording

Another wholly-owned product candidate is CX-801, an interferon ("IFN") alpha-2b PROBODY. IFNα2b provides a potentially superior approach to activating anti-tumor immune responses than other cytokines. CX-801 is a dually masked, conditionally activated version of IFNα2b that has the potential to become a cornerstone of combination therapy for a wide range of tumor types. The IND for CX-801 was cleared by the FDA in January 2024, and in June 2024 the first clinical site for the CX-801 Phase 1 dose escalation study in solid tumors was activated. The Phase 1 dose escalation study will enroll patients with melanoma, renal cell carcinoma, and head and neck squamous cell carcinoma. In Phase 1 dose escalation, we will evaluate safety and signs of clinical activity for CX-801 monotherapy and in combination with KEYTRUDA®. In second quarter of 2024, CytomX announced a clinical collaboration with Merck to supply KEYTRUDA for evaluation of CX-801 in combination with KEYTRUDA® in the Phase 1 study.

Previous wording

CX-2029 was previously developed in a global co-development collaboration with AbbVie. This program is intended to open a therapeutic window for successful targeting of CD71, also known as the transferrin receptor 1 (“TfR1”). CD71 is a cell surface protein essential for iron uptake in dividing cells and is highly expressed in a number of solid and hematologic cancers. However, given its central role in iron metabolism, CD71 is present on most healthy cells and is thought to be an undruggable target with conventional ADCs. CX-2029 is conjugated with the tubulin inhibitor, monomethyl auristatin E (“MMAE”), as the payload. In March 2023, following the completion of the Phase 2 Study in squamous non-small cell lung cancer (“sqNSCLC”), head and neck squamous cell carcinoma (“HNSCC”), esophageal and gastro-esophageal junction (“E/GEJ”) cancers, AbbVie notified CytomX that it would not advance CX-2029 into additional clinical studies and terminated the 2016 CD71 License and Collaboration Agreement. CytomX re-acquired full rights to CX-2029 but does not currently have plans to make further significant investments in the solid tumor program in the near-term but continues to view CD71 as a target of strategic interest, including novel next-generation strategies.

Current wording

CX-2029 was previously developed in a global co-development collaboration with AbbVie. This program is intended to open a therapeutic window for successful targeting of CD71, also known as the transferrin receptor 1 (“TfR1”). CD71 is a cell surface protein essential for iron uptake in dividing cells and is highly expressed in a number of solid and hematologic cancers. However, given its central role in iron metabolism, CD71 is present on most healthy cells and is thought to be an undruggable target with conventional ADCs. CX-2029 is conjugated with the tubulin inhibitor, monomethyl auristatin E (“MMAE”), as the payload. In March 2023, following the completion of the Phase 2 Study in squamous non-small cell lung cancer (“sqNSCLC”), head and neck squamous cell carcinoma (“HNSCC”), esophageal and gastro-esophageal junction (“E/GEJ”) cancers, AbbVie notified CytomX that it would not advance CX-2029 into additional clinical studies and terminated the 2016 CD71 License and Collaboration Agreement. CytomX re-acquired full rights to CX-2029 but does not currently have

Previous wording

We do not have any products approved for sale, and we continue to incur significant research and development and general administrative expenses related to our operations. As of March 31, 2024 and December 31, 2023, we had an accumulated deficit of $709.7 million and $723.4 million, respectively.

Current wording

We do not have any products approved for sale, and we continue to incur significant research and development and general administrative expenses related to our operations. As of June 30, 2024 and December 31, 2023, we had an accumulated deficit of $716.2 million and $723.4 million, respectively.

Previous wording

We also account for uncertain tax positions in accordance with the provisions of ASC 740. When uncertain tax positions exist, we recognize the tax benefit of tax positions to the extent that the benefit will more likely than not be realized. The determination as to whether the tax benefit will more likely than not be realized is based upon the technical merits of the tax position as well as consideration of the available facts and circumstances.

Current wording

We also account for uncertain tax positions in accordance with the provisions of ASC 740. When uncertain tax positions exist, we recognize the tax benefit of tax positions to the extent that the benefit will be more likely than not be realized. The determination as to whether the tax benefit will more likely than not be realized is based upon the technical merits of the tax position as well as consideration of the available facts and circumstances.

Previous wording

The increase in revenue of $18.0 million for the three months ended March 31, 2024 compared to the corresponding period of 2023 was primarily due to:

Current wording

The increase in revenue of $18.4 million for the six months ended June 30, 2024 compared to the corresponding period of 2023 was primarily due to:

Previous wording

An increase in revenue under the Astellas Agreement primarily driven by two milestone payments of $5.0 million each, triggered in March 2024. One was related to the nomination of a second clinical candidate while the other was related to the milestone achievement of GLP toxicology study of the first clinical candidate. Astellas revenue in the first quarter of 2023 included the $5.0 million milestone for the 1st clinical candidate nomination achieved in the collaboration;

Current wording

An increase in revenue under the Astellas Agreement primarily driven by two milestone payments of $5.0 million each, triggered in March 2024. One was related to the nomination of a second clinical candidate while the other was related to the milestone achievement of GLP toxicology study initiation for the first clinical candidate. Astellas revenue in the first quarter of 2023 included the $5.0 million milestone for the 1st clinical candidate nomination achieved in the collaboration;

Previous wording

Research and development expenses increased by $0.9 million for the three months ended March 31, 2024, compared to 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.

Current wording

decrease in laboratory contract services and manufacturing activities for the CX-801 program and winding down of clinical study activities related to the CX-2029 and CX-2009 programs.

Previous wording

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

Current wording

General and administrative expenses increased by $0.8 million for the six months ended June 30, 2024, compared to the corresponding period of 2023, primarily due to higher consulting expenses, personnel related expenses and intellectual property related legal services expenses partially offset by lower rent as a result of partial sublease of the Company’s headquarters started in March 2023.

Previous wording

The $0.1 million tax provision represented the interest accrued for the three months ended March 31,2024 related to the proposed assessment received from the state of California for the years 2017 and 2018.

Current wording

The $0.1 million and $0.1 million tax provision represented the interest accrued for the three and six months ended June 30, 2024, respectively, related to the proposed assessment received from the state of California for the years 2017 and 2018.

Previous wording

As of March 31, 2024, we had cash, cash equivalents and short-term investments of $150.3 million and an accumulated deficit of $709.7 million, compared to cash, cash equivalents and short-term investments of $174.5 million and an accumulated deficit of $723.4 million as of December 31, 2023. To date, we have financed our operations primarily through sales of our common stock in conjunction with the IPO, subsequent stock offerings and through our at-the-market offering, sales of our convertible preferred securities prior to our IPO, payments received under our collaboration agreements and proceeds from private placements of our common stock, warrants and pre-funded warrants. In July 2023, we completed a private placement and issued pre-funded warrants to purchase an aggregate of 14,423,077 shares of common stock, accompanying Tranche 1 warrants to purchase up to 5,769,231 shares of common stock and accompanying Tranche 2 warrants to purchase up to 5,769,231 shares of common stock, at a combined price of $2.08 per share. We received gross proceeds of approximately $30.0 million. In March 2024, we achieved a clinical candidate milestone for a second collaboration target as well as the GLP toxicology studies milestone for the first collaboration target nominated in January 2023 under the Astellas Agreement. We collected the two milestones payment totaled $10.0 million in April 2024. In April 2024, we sold 2,270,608 shares at an average price of $2.20 per share under our at-the-market offering and received net proceeds of approximately $4.8 million after deducting the 3.0% sales commission and related issuance cost.

Current wording

As of June 30, 2024, we had cash, cash equivalents and short-term investments of $137.2 million and an accumulated deficit of $716.2 million, compared to cash, cash equivalents and short-term investments of $174.5 million and an accumulated deficit of $723.4 million as of December 31, 2023. To date, we have financed our operations primarily through sales of our common stock in conjunction with the IPO, subsequent stock offerings and through our at-the-market offering, sales of our convertible preferred securities prior to our IPO, payments received under our collaboration agreements and proceeds from private placements of our common stock, warrants and pre-funded warrants. In July 2023, we completed a private placement and issued pre-funded warrants to purchase an aggregate of 14,423,077 shares of common stock, accompanying Tranche 1 warrants to purchase up to 5,769,231 shares of common stock and accompanying Tranche 2 warrants to purchase up to 5,769,231 shares of common stock, at a combined price of $2.08 per share. We received gross proceeds of approximately $30.0 million. In March 2024, we achieved a clinical candidate milestone for a second collaboration target as well as the GLP toxicology studies milestone for the first collaboration target nominated in January 2023 under the Astellas Agreement. We collected the two milestones payment totaled $10.0 million in April 2024. In April 2024, we sold 2,270,608 shares at an average price of $2.20 per share under our at-the-market offering and received net proceeds of approximately $4.8 million after deducting the 3.0% sales commission and related issuance cost.

Previous wording

Factors” in this Quarterly Report on Form 10-Q. The cost and timing of developing our product candidates is highly uncertain and subject to substantial risks and changes. As such, we may alter our expenditures as a result of contingencies such as the failure of one or all of our product candidates currently in clinical development, the acceleration of one or all of our product candidates in clinical development, the initiating of clinical trials for additional product candidates, the identification of more promising product candidates in our research efforts or unexpected operating costs and expenditures. We will need to raise additional funds in the future. There can be no assurance, however, that such efforts will be successful; or if they are successful, that the terms and conditions of such financing will be favorable to us.

Current wording

Based upon our current operating plan, we expect our existing capital resources will be sufficient to fund operations to the end of 2025. However, if the anticipated operating results and future financing are not achieved in future periods, our planned expenditures may need to be reduced in order to extend the time period over which the then-available resources would be able to fund the operations. The amounts and timing of our actual expenditures depend on numerous factors, including the progress of our preclinical and clinical development efforts, the results of any clinical trials and other studies, our operating costs and expenditures and other factors described under the caption “Risk Factors” in this Quarterly Report on Form 10-Q. The cost and timing of developing our product candidates is highly uncertain and subject to substantial risks and changes. As such, we may alter our expenditures as a result of contingencies such as the failure of one or all of our product candidates currently in clinical development, the acceleration of one or all of our product candidates in clinical development, the initiating of clinical trials for additional product candidates, the identification of more promising product candidates in our research efforts or unexpected operating costs and expenditures. We will need to raise additional funds in the future. There can be no assurance, however, that such efforts will be successful; or if they are successful, that the terms and conditions of such financing will be favorable to us.

Previous wording

During the three months ended March 31, 2024, cash used in operating activities was $26.0 million, which consisted of a net income of $13.8 million and non-cash charges of $1.5 million, adjusted by a net decrease of $41.3 million relating to the change of our net operating assets and liabilities. The non-cash charges primarily consisted of $1.9 million in stock-based compensation, $1.0 million in non-cash lease expense, $0.5 million in depreciation and amortization, partially offset by $1.9 million in accretion of discounts on investments.

Current wording

During the six months ended June 30, 2024, cash used in operating activities was $45.6 million, which consisted of a net income of $7.3 million and non-cash charges of $3.4 million, adjusted by a net decrease of $56.3 million relating to the change of our net operating assets and liabilities. The non-cash charges primarily consisted of $3.8 million in stock-based compensation, $2.0 million in non-cash lease expense, $0.9 million in depreciation and amortization, partially offset by $3.3 million in accretion of discounts on investments.

Previous wording

a net decrease of $28.9 million in deferred revenue resulting from the continued recognition of deferred revenue from existing customers;

Current wording

a net decrease of $51.8 million in deferred revenue resulting from the continued recognition of deferred revenue from existing customers;

Previous wording

a decrease of $3.9 million in accounts payable, accrued and other long-term liabilities primarily due to timing of payments;

Current wording

a decrease of $7.0 million in accounts payable, accrued and other long-term liabilities primarily due to timing of payments; offset by

Previous wording

an increase $1.2 million in cashflows from prepaid and other current assets primarily due to decrease in advance payments due to timing of payment.

Current wording

an increase of $2.5 million in cashflows from accounts receivable, prepaid and other current assets primarily due to decrease in advance payments due to timing of payment.

Previous wording

During the three months ended March 31, 2023, cash provided by operating activities was $9.4 million, which consisted of a net loss of $3.3 million, adjusted by non-cash charges of $2.4 million and a net increase of $10.3 million relating to the change of our net operating assets and liabilities. The non-cash charges primarily consisted of $2.4 million in stock-based compensation, $0.9 million in non-cash lease expense, $0.6 million in depreciation and amortization, partially offset by $1.5 million in accretion of discounts on investments.

Current wording

During the six months ended June 30, 2023, cash used in operating activities was $15.8 million, which consisted of a net loss of $4.4 million, adjusted by non-cash charges of $4.6 million and a net decrease of $16.0 million relating to the change of our net operating assets and liabilities. The non-cash charges primarily consisted of $4.8 million in stock-based compensation, $1.8 million in non-cash lease expense, $1.2 million in depreciation and amortization, partially offset by $3.2 million in accretion of discounts on investments.

Previous wording

a net decrease of $17.4 million in deferred revenue resulting from the continued recognition of deferred revenue from existing and new customers;

Current wording

a net decrease of $40.2 million in deferred revenue resulting from the continued recognition of deferred revenue from existing and new customers;

Previous wording

a decrease of $8.0 million in accounts payable, accrued and other long-term liabilities primarily due to decrease of payroll-related expenses and restructuring related expenses as well as timing of other payments; offset by

Current wording

a decrease of $12.3 million in accounts payable, accrued and other long-term liabilities primarily due to decrease of payroll-related expenses and restructuring related expenses as well as timing of other payments; offset by

Previous wording

an increase of $34.9 million in cash flows from accounts receivable primarily related to the receipt of the $35.0 million upfront payment and prepaid research under the Moderna agreement entered into in December 2022.

Current wording

an increase of $34.1 million in cash flows from accounts receivable primarily related to the receipt of the $35.0 million upfront payment and prepaid research under the Moderna agreement entered into in December 2022.

Previous wording

a increase $0.8 million in cashflows from prepaid and other current assets primarily due to decrease in advance payments to our third party manufacturing vendors and timing of payments.

Current wording

an increase of $2.4 million in cashflows from prepaid and other current assets primarily due to a decrease in advance payments to our third party manufacturing vendors and timing of payments.

Previous wording

During the three months ended March 31, 2024, cash provided by investing activities was $44.9 million consisted of $45.0 million of proceeds from the maturities of short-term investments partially offset by $0.1 million of capital expenditures used to purchase property and equipment.

Current wording

During the six months ended June 30, 2024, cash provided by investing activities was $66.4 million, which consisted of $160.0 million of proceeds from the maturities of short-term investments partially offset by $93.4 million used in the purchase of short-term investments and $0.2 million of capital expenditures used to purchase property and equipment.

Previous wording

During the three months ended March 31, 2024, cash provided by financing activities was $0.2 million consisted of proceeds from the exercise of stock options.

Current wording

During the six months ended June 30, 2023, cash provided by financing activities consisted of $0.3 million of proceeds from the exercise of stock options and employee stock purchases under the employee stock purchase plan.

Previous wording

During the three months ended March 31, 2024, there were no material changes in contractual obligations from the amounts disclosed in our Annual Report on Form 10-K for the year ended December 31, 2023.

Current wording

During the six months ended June 30, 2024, there were no material changes in contractual obligations from the amounts disclosed in our Annual Report on Form 10-K for the year ended December 31, 2023.