CytomX Therapeutics Inc

Previous wording

Our proprietary, versatile, multi-modality PROBODY technology platform is designed to enable conditional activation of potent biologic therapeutic candidates within the tumor microenvironment, while minimizing drug activity in healthy tissues and circulation. Our platform is built on a strong foundation of tumor biology expertise, including deep knowledge of tumor-associated enzymes known as proteases. Proteases are tightly controlled in normal tissues but often dysregulated and active in tumor microenvironments where they play important roles in cancer cell migration, invasion and metastasis. Leveraging our deep scientific knowledge, we conceived of and constructed our PROBODY therapeutic platform which allows us to genetically engineer biologic therapeutic candidates to contain protease-cleavable masks. Our masking strategy is designed to reduce binding of biologic therapeutics to their targets until the mask is removed by proteases in the tumor microenvironment, providing more selective targeting of the tumor.

Current wording

Our proprietary, versatile, multi-modality PROBODY technology platform is designed to enable conditional activation of potent masked biologic therapeutic candidates within the tumor microenvironment, while minimizing drug activity in healthy tissues and circulation. Our platform is built on a strong foundation of tumor biology expertise, including deep knowledge of tumor-associated enzymes known as proteases. Proteases are tightly controlled in normal tissues but often dysregulated and active in tumor microenvironments where they play important roles in cancer cell migration, invasion and metastasis. Leveraging our deep scientific knowledge, we conceived of and constructed our PROBODY therapeutic platform which allows us to genetically engineer biologic therapeutic candidates to contain protease-cleavable masks. Our masking strategy is designed to reduce binding of biologic therapeutics to their targets until the mask is removed by proteases in the tumor microenvironment, providing more selective targeting of the tumor.

Previous wording

Reinforcing our leadership in the field of conditional activation, in 2022 we advanced our first TCE into the clinic. CX-904, partnered with Amgen, is a conditionally activated TCE against EGFR and CD3. In preclinical studies, CytomX’s PROBODY EGFRxCD3 TCE demonstrated anti-tumor activity and better tolerability when compared to TCEs without PROBODY masking. In May 2022, the first patient was dosed in a Phase 1 study evaluating CX-904 as a treatment for patients with advanced solid tumors. Patient enrollment in the Phase 1 dose escalation portion of the study continues to progress. We reported in January 2023 that the initial single patient cohort phase of the study was complete and that the “3+3” patient cohort phase had been initiated.

Current wording

Reinforcing our leadership in the field of conditional activation, in 2022 we advanced our first TCE into the clinic. CX-904, partnered with Amgen, is a conditionally activated TCE against EGFR and CD3. In preclinical studies, CytomX’s PROBODY EGFRxCD3 TCE demonstrated anti-tumor activity and better tolerability when compared to TCEs without PROBODY masking. In May 2022, the first patient was dosed in a Phase 1 study evaluating CX-904 as a treatment for patients with advanced solid tumors. Patient enrollment in the Phase 1 dose escalation portion of the study continues to progress.

Previous 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.

Current wording

Our pipeline also includes CX-2051, a wholly-owned conditionally activated, PROBODY ADC directed toward the epithelial cell adhesion molecule (EpCAM). The CX-2051 payload, a next generation topoisomerase-1 inhibitor payload licensed from AbbVie (formerly ImmunoGen), is tailored to specific EpCAM-expressing indications, including colorectal cancer, and includes a payload-antibody linker designed to drive bystander effect, contributing to anti-tumor activity. The design of 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. 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.

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 a primary initial focus in CRC commenced in April 2024. As of November 2024, the Phase 1 study is enrolling the fifth dose escalation cohort with favorable safety and tolerability having been observed to date. High expression of EpCAM has been documented in many tumor types, including colorectal cancer. In the Phase 1 study, EpCAM expression levels are being assessed retrospectively and are anticipated to be high in the majority of CRC patients. The Phase 1 dose escalation is intended to demonstrate clinical proof of concept to potentially move into dose expansion studies in 2025. Dose escalation enrollment continues with initial Phase 1 data for CX-2051 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 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.

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 the third quarter of 2024 the first patient was dosed in the CX-801 Phase 1 dose escalation study in solid tumors. The Phase 1 dose escalation study will enroll patients primarily with melanoma as well as renal cell carcinoma and head and neck squamous cell carcinoma. In Phase 1 dose escalation, the study 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

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 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.

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 June 30, 2024 and December 31, 2023, we had an accumulated deficit of $716.2 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 September 30, 2024 and December 31, 2023, we had an accumulated deficit of $710.5 million and $723.4 million, respectively.

Previous 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:

Current wording

The increase in revenue of $25.4 million for the nine months ended September 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 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;

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 first clinical candidate nomination achieved in the collaboration;

Previous wording

Research and development expenses increased by $4.5 million and $5.4 million for the three and six months ended June 30, 2024 compared to the corresponding periods of 2023. This was primarily due to:

Current wording

Research and development expenses increased by $4.9 million for the three months ended September 30, 2024 compared to the corresponding period of 2023. This was primarily due to:

Previous wording

increase in manufacturing activities for the CX-2051 program and clinical trial activities for the CX-904 program;

Current wording

increase in manufacturing and clinical related activities for the CX-2051 program and clinical trial activities for the CX-904 program;

Previous 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.

Current wording

decrease in manufacturing activities and laboratory contract services 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 increased by $1.0 million for the three 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.

Current wording

General and administrative expenses increased by $1.1 million for the three months ended September 30, 2024, compared to the corresponding period of 2023, primarily due to higher professional service expenses supporting intellectual property related activities and internal controls.

Previous 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.

Current wording

General and administrative expenses increased by $1.9 million for the nine months ended September 30, 2024, compared to the corresponding period of 2023, primarily due to higher professional services spend supporting intellectual property related activities and internal controls, and consulting and personnel related expenses, partially offset by lower rent as a result of partial sublease of the Company’s headquarters which started in March 2023.

Previous wording

Interest income decreased by $0.3 million and $0.5 million for the three and six months ended June 30, 2024, respectively, compared to the corresponding periods of 2023 was primarily driven by lower interest rates and the lower cash and cash equivalents and short-term investments position as compared to the corresponding periods.

Current wording

Interest income decreased by $1.0 million and $1.5 million for the three and nine months ended September 30, 2024, respectively, compared to the corresponding periods of 2023. The decrease was primarily driven by lower interest rates and the lower cash and cash equivalents and short-term investments position as compared to the corresponding periods of 2023.

Previous 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.

Current wording

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

Previous 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.

Current wording

As of September 30, 2024, we had cash, cash equivalents and short-term investments of $117.6 million and an accumulated deficit of $710.5 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. During the three months ended September 30, 2024, we did not sell any shares of common stock under our at-the-market offering program. As of September 30, 2024, $58.3 million remained available for sale under the Sales Agreement.

Previous 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.

Current wording

During the nine months ended September 30, 2024, cash used in operating activities was $66.3 million, which consisted of a net income of $13.0 million and non-cash charges of $5.6 million, adjusted by a net decrease of $84.9 million relating to the change of our net operating assets and liabilities. The non-cash charges primarily consisted of $5.8 million in stock-based compensation, $3.0 million in non-cash lease expense, $1.3 million in depreciation and amortization, partially offset by $4.5 million in accretion of discounts on investments.

Previous wording

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

Current wording

a net decrease of $82.7 million in deferred revenue resulting from the continued recognition of deferred revenue from existing customers;

Previous wording

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

Current wording

a decrease of $4.1 million in accounts payable, accrued and other long-term liabilities primarily due to timing of payments; offset by

Previous 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.

Current wording

an increase of $1.9 million in cashflows from accounts receivable, prepaid and other current assets primarily due to decrease in advance payments.

Previous 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.

Current wording

During the nine months ended September 30, 2023, cash used in operating activities was $34.1 million, which consisted of a net loss of $1.4 million and a net decrease of $38.0 million relating to the change of our net operating assets and liabilities, offset by non-cash charges of $5.3 million. The non-cash charges primarily consisted of $6.0 million in stock-based compensation, $2.8 million in non-cash lease expense, $1.7 million in depreciation and amortization, partially offset by $5.2 million in accretion of discounts on investments.

Previous wording

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

Current wording

a net decrease of $64.7 million in deferred revenue resulting from the continued recognition of deferred revenue from existing and new customers;

Previous 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

Current wording

a decrease of $9.6 million in accounts payable, accrued and other long-term liabilities primarily due to decrease of payroll-related expenses, restructuring related expenses, and laboratory contract services; offset by

Previous 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.

Current wording

an increase of $33.6 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

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.

Current wording

an increase of $2.7 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 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.

Current wording

During the nine months ended September 30, 2024, cash provided by investing activities was $84.6 million, which consisted of 190.5 million of proceeds from the maturities of short-term investments partially offset by $105.7 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 six months ended June 30, 2023, cash used in investing activities was $120.6 million, which consisted of $220.0 million used in the purchase of short-term investments and $0.6 million of capital expenditures used to purchase property and equipment, partially offset by $100.0 million in proceeds received upon the maturity of marketable securities.

Current wording

During the nine months ended September 30, 2023, cash used in investing activities was $163.5 million, which consisted of $313.0 million used in the purchase of short-term investments and $0.5 million of capital expenditures used to purchase property and equipment, partially offset by $150.0 million in proceeds received upon the maturity of marketable securities.

Previous wording

During the six months ended June 30, 2024, cash provided by financing activities was $5.2 million, which consisted of $4.8 million of net proceeds from issuance of common stock, net of issuance costs and $0.4 million of proceeds from the exercise of stock options and employee stock purchases under the employee stock purchase plan.

Current wording

During the nine months ended September 30, 2024, cash provided by financing activities was $5.3 million, which consisted of $4.8 million of net proceeds from issuance of common stock, net of issuance costs, and $0.4 million of proceeds from the exercise of stock options and employee stock purchases under the employee stock purchase plan.

Previous 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.

Current wording

During the nine months ended September 30, 2023, cash provided by financing activities consisted of $29.7 million of net proceeds from issuance of pre-funded warrants and warrants and $0.4 million of proceeds from the exercise of stock options and employee stock purchases under the employee stock purchase plan.

Previous 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.

Current wording

During the nine months ended September 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.