Acrivon Therapeutics, Inc.

Previous wording

The ACR-368 registrational intent multi-center Phase 2B trial is based on OncoSignature-predicted sensitivity to ACR-368 in endometrial cancer patients, a tumor type predicted to be sensitive to ACR-368 through preclinical AP3-based indication finding, and not previously evaluated in past clinical trials. Our ACR-368 OncoSignature test, which has not yet obtained regulatory approval, has been extensively evaluated in preclinical studies, including in two separate, blinded, prospectively-designed studies on pretreatment tumor biopsies collected from patients with ovarian cancer treated with ACR-368 in past Phase 2 clinical trials conducted by Lilly and at the National Cancer Institute providing evidence of robust enrichment of responders through our method. Moreover, the ongoing registrational intent trial in endometrial cancer showed initial validation of the ACR-368 OncoSignature for prospective patient selection. Based on these sets of data, the U.S. Food and Drug Administration, or FDA, has granted Breakthrough Device designations for the ACR-368 OncoSignature assay for the identification of ovarian cancer patients who may benefit from ACR-368 treatment and for the identification of endometrial cancer patients who may benefit from ACR-368 treatment.

Current wording

The ACR-368 registrational-intent multi-center Phase 2B trial is based on OncoSignature-predicted sensitivity to ACR-368 in endometrial cancer patients, a tumor type predicted to be sensitive to ACR-368 through preclinical AP3-based indication finding, and not previously evaluated in past clinical trials. Our ACR-368 OncoSignature test, which has not yet obtained regulatory approval, has been extensively evaluated in preclinical studies, including in two separate, blinded, prospectively-designed studies on pretreatment tumor biopsies collected from patients with ovarian cancer treated with ACR-368 in past Phase 2 clinical trials conducted by Lilly and at the National Cancer Institute providing evidence of robust enrichment of responders through our method. Moreover, the ongoing registrational-intent trial in endometrial cancer showed initial validation of the ACR-368 OncoSignature for prospective patient selection.

Previous wording

An interim data extract from the EDC clinical database was done on February 25, 2025, including 20 BM+ endometrial cancer patients treated with ACR-368 monotherapy and 38 OncoSignature-negative, or BM-, treated with ACR-368 plus ultra low-dose gemcitabine, or ULDG, that were efficacy-evaluable by RECIST (2 BM- had treatment discontinued without scan). All BM+ patients had progressed after prior platinum-based chemotherapy and prior anti-PD-1, and the median and mean prior lines of therapy for these patients were 2 and 2.6, respectively. A majority of these BM+ patients were refractory to the last prior line of therapy, with aggressive, generally heavily pre-treated tumors: 12 had refractory disease (best overall response of progressive disease in the last prior line of therapy), 6 had relapsed disease, and 2 unknown. Amongst these 20 BM+ patients, 15 were either serous or carcinosarcomas, 13 were pMMR (2 dMMR, 5 not tested), and 11 p53 mutated (3 wild-type; 6 unknown). In patients that had relapsed after the prior line of therapy (N=6), the confirmed overall response rate, or ORR, was 50% and the disease control rate, or DCR, was 100%. Amongst the 12 patients with tumors refractory to the last prior line of therapy (ORR = 0%) we observed meaningful ACR-368 clinical activity with a confirmed ORR of 33% and DCR of 75%. The ACR-368 OncoSignature accurately identified patients whose tumors are sensitive to ACR-368, with 80% of BM+ patients demonstrating tumor shrinkage. Among all 20 BM+ patients the confirmed ORR was 35% and the DCR was 80% with median duration of response >5.6 months (not yet reached). Overall, we observed significant anti-tumor activity and disease control in BM+ patients with aggressive, refractory tumors that did not respond at all (0 % ORR) to the last line of prior therapy, and with a confirmed ORR more than double (35%) the best ORR observed in the last prior line of therapy (15%) for all BM+ patients.

Current wording

An interim data extract from the EDC clinical database was done on February 25, 2025, including 20 BM+ endometrial cancer patients treated with ACR-368 monotherapy and 38 OncoSignature-negative, or BM-, treated with ACR-368 plus ultra low-dose gemcitabine, or ULDG, that were efficacy-evaluable by RECIST (2 BM- had treatment discontinued without scan). All BM+ patients had progressed after prior platinum-based chemotherapy and prior anti-PD-1, and the median and mean prior lines of therapy for these patients were 2 and 2.6, respectively. Based on available EDC data, a majority of these BM+ patients were refractory to the last prior line of therapy, with aggressive, generally heavily pre-treated tumors: 12 had refractory disease (best overall response of progressive disease in the last prior line of therapy), 6 had relapsed disease, and 2 unknown. Amongst these 20 BM+ patients, 15 were either serous or carcinosarcomas, 13 were pMMR (2 dMMR, 5 not tested), and 11 p53 mutated (3 wild-type; 6 unknown). In patients that had relapsed after the prior line of therapy (N=6), the confirmed overall response rate, or ORR, was 50% and the disease control rate, or DCR, was 100%. Amongst the 12 patients with tumors refractory to the last prior line of therapy (ORR = 0%) we observed meaningful ACR-368 clinical activity with a confirmed ORR of 33% and DCR of 75%. The ACR-368 OncoSignature accurately identified patients whose tumors are sensitive to ACR-368, with 80% of BM+ patients demonstrating tumor shrinkage. Among all 20 BM+ patients the confirmed ORR was 35% and the DCR was 80% with median duration of response >5.6 months (not yet reached). Overall, we observed significant anti-tumor activity and disease control in BM+ patients with aggressive, refractory tumors that did not respond at all (0 % ORR) to the last line of prior therapy, and with a confirmed ORR more than double (35%) the best ORR observed in the last prior line of therapy (15%) for all BM+ patients.

Previous wording

We are also leveraging our proprietary AP3 precision medicine platform for streamlined drug discovery through AP3-based drug optimization in intact cells and co-crystallography and to develop our internally-discovered pipeline programs. ACR-2316, our second clinical stage asset, is a novel, selective WEE1/PKMYT1 inhibitor designed using AP3 for superior single-agent activity through strong activation of not only CDK1 and CDK2 but also of PLK1 to drive pro-apoptotic cell death, as observed in preclinical studies against benchmark inhibitors. Utilizing AP3, we were able to advance ACR-2316 to first dosing in a Phase 1 trial in 15 months, with dosing initiated in the third quarter of 2024. The Phase 1 study will assess the safety and tolerability of ACR-2316. Additionally, the study will seek to establish the pharmacokinetic, or PK, profile, evaluate preliminary anti-tumor activity and determine the recommended Phase 2 monotherapy dose. Dose optimization is being guided by drug target engagement in alignment with the FDA’s Project Optimus. We anticipate providing a clinical data update in the second half of 2025. Based on PK analysis we have observed encouraging approximate dose proportionality in the first two dose level, or DL, cohorts. Moreover, using our internal MS-based AP3 profiling to support the clinical trial of ACR-2316, we have observed significant drug target engagement in peripheral blood mononuclear cells already at DL 1. In addition, initial clinical activity has been observed in several solid tumor types including an ongoing confirmed partial response in an endometrial cancer patient who had received three prior lines of therapy including chemotherapy and anti-PD-1 at DL3, with significant decrease in size of metastatic lesions throughout the chest, abdomen and pelvis at first scan. In addition, we are advancing a preclinical program directed against an undisclosed cell cycle regulatory target, with a development candidate nomination anticipated in 2025.

Current wording

We are also leveraging our proprietary AP3 precision medicine platform for streamlined drug discovery through AP3-based drug optimization in intact cells and co-crystallography and to develop our internally-discovered pipeline programs. ACR-2316, our second clinical stage asset, is a novel, selective WEE1/PKMYT1 inhibitor designed using AP3 for superior single-agent activity through strong activation of not only CDK1 and CDK2 but also of PLK1 to drive pro-apoptotic cell death, as observed in preclinical studies against benchmark inhibitors. Utilizing AP3, we were able to advance ACR-2316 to first dosing in a Phase 1 trial in 15 months, with dosing initiated in the third quarter of 2024. The Phase 1 study will assess the safety and tolerability of ACR-2316. Additionally, the study will seek to establish the pharmacokinetic, or PK, profile, evaluate preliminary anti-tumor activity and determine the recommended Phase 2 monotherapy dose. Dose optimization is being guided by drug target engagement in alignment with the FDA’s Project Optimus. We anticipate providing a clinical data update in the second half of 2025. Based on PK analysis we have observed encouraging approximate dose proportionality in the first two dose level, or DL, cohorts. Moreover, using our internal MS-based AP3 profiling to support the clinical trial of ACR-2316, we have observed significant drug target engagement in peripheral blood mononuclear cells already at DL 1. In addition, initial clinical activity with tumor shrinkage has been observed across several solid tumor types predicted to be sensitive to ACR-2316 by AP3 during our dose escalation phase, including a confirmed partial response already at DL3, which is well below the anticipated RP2D. In addition, we are advancing a preclinical program directed against an undisclosed cell cycle regulatory target, with a development candidate nomination anticipated in 2025.

Previous wording

We have established the Generative Phosphoproteomics AP3 platform which is designed to allow us to interpret and quantify the drug-regulated pathway activity levels inside the intact cell. The Generative Phosphoproteomics AP3 platform is comprised of a growing suite of powerful, internally developed tools, including the AP3 Interactome, the AP3 Kinase Substrate Relationship Predictor, the AP3 Data Portal, designed to enable the conversion of multimodal data into structured data amenable for generative AI analyses, and the AP3 Chatbot. Through the combination of these distinctive tools and capabilities, the platform enables us to go beyond current AI target-centric drug discovery and to rapidly design highly differentiated compounds for streamlined clinical development via the integrated analyses of the generated datasets through a unified computational interface.

Current wording

We have established the Generative Phosphoproteomics AP3 platform which is designed to allow us to interpret and quantify the drug-regulated pathway activity levels inside the intact cell. The Generative Phosphoproteomics AP3 platform is comprised of a growing suite of powerful, internally developed tools, including the AP3 Interactome, the AP3 Kinase Substrate Relationship Predictor, the AP3 Data Portal, designed to enable the conversion of multimodal data into structured data amenable for generative AI analyses, and the AP3 Chatbot. Through the combination of these distinctive tools and capabilities, the platform enables us to go beyond current AI target-centric drug discovery and to rapidly design highly differentiated compounds with optimal, desirable pathway effects on the intracellular signaling network to mechanistically address the underlying molecular cause of disease. The integrated analyses of our AP3generated proprietary datasets through a unified computational interface enables streamlined transition from preclinical to the clinical phase, as exemplified by the development of ACR-2316.

Previous wording

We have incurred recurring operating losses since inception. Our net losses for the six months ended June 30, 2025 and 2024 were $40.7 million and $35.3 million, respectively. As of June 30, 2025, we had an accumulated deficit of $237.7 million. These losses have resulted primarily from costs incurred in connection with research and development activities and general and administrative costs associated with our operations. We expect to continue to incur significant and increasing expenses and operating losses for the foreseeable future, particularly if and as we:

Current wording

We have incurred recurring operating losses since inception. Our net losses for the nine months ended September 30, 2025 and 2024 were $58.9 million and $57.7 million, respectively. As of September 30, 2025, we had an accumulated deficit of $255.9 million. These losses have resulted primarily from costs incurred in connection with research and development activities and general and administrative costs associated with our operations. We expect to continue to incur significant and increasing expenses and operating losses for the foreseeable future, particularly if and as we:

Previous wording

As of June 30, 2025, we had cash, cash equivalents and investments of $147.6 million. We believe that our existing cash, cash equivalents and investments as of June 30, 2025, will enable us to fund our operating expenses and capital expenditure requirements into the second quarter of 2027. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. See the section titled “—Liquidity and Capital Resources.”

Current wording

As of September 30, 2025, we had cash, cash equivalents and investments of $134.4 million. We believe that our existing cash, cash equivalents and investments as of September 30, 2025, will enable us to fund our operating expenses and capital expenditure requirements into the second quarter of 2027. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. See the section titled “—Liquidity and Capital Resources.”

Previous wording

In June 2022, we entered into a companion diagnostic agreement, or the Akoya Agreement, with Akoya Biosciences, Inc., or Akoya, pursuant to which we agreed to co-develop, validate, and commercialize our proprietary ACR-368 OncoSignature test, the companion diagnostic that will be used to identify patients with cancer most likely to respond to ACR-368.

Current wording

In June 2022, we entered into a companion diagnostic agreement, or the Akoya Agreement, with Akoya Biosciences, Inc., or Akoya, pursuant to which we agreed to co-develop, validate, and commercialize our proprietary ACR-368 OncoSignature test, the companion diagnostic that will be used to identify patients with endometrial cancer most likely to respond to ACR-368.

Previous wording

Pursuant to the agreement, as subsequently amended, we paid Akoya a one-time, non-refundable, non-creditable upfront payment in the amount of $0.6 million. We are obligated to pay Akoya up to an aggregate of $20.3 million upon the achievement of specified development and pre-commercialization milestones. As of August 13, 2025, development and pre-commercialization milestones totaling $18.2 million have been achieved by Akoya under the agreement. Other than certain specified pass-through costs, each party is responsible for its own costs associated with the development of the companion diagnostic. Akoya will procure and manufacture necessary supplies to perform the ACR-368 OncoSignature test to support our clinical development and commercial requirements, in accordance with a supply agreement to be mutually agreed upon by the parties. We may terminate the agreement at our convenience, subject to the payment of a termination fee in the amount of $1.0 million.

Current wording

Pursuant to the agreement, as subsequently amended, we paid Akoya, now a wholly owned subsidiary of Quanterix Corporation, a one-time, non-refundable, non-creditable upfront payment in the amount of $0.6 million. We are obligated to pay Akoya up to an aggregate of $20.3 million upon the achievement of specified development and pre-commercialization milestones. As of November 13, 2025, development and pre-commercialization milestones totaling $18.2 million have been achieved by Akoya under the agreement. Other than certain specified pass-through costs, each party is responsible for its own costs associated with the development of the companion diagnostic. Akoya will procure and manufacture necessary supplies to perform the ACR-368 OncoSignature test to support our clinical development and commercial requirements, in accordance with a supply agreement to be mutually agreed upon by the parties. We may terminate the agreement at our convenience, subject to the payment of a termination fee in the amount of $1.0 million.

Previous wording

We anticipate that our general and administrative expenses will continue to increase in the future as we increase our headcount to support our continued research activities and development of our drug candidates. We also anticipate that we will continue to incur significant accounting, audit, legal, regulatory, compliance and director and officer insurance costs, as well as investor and public relations expenses associated with operating as a public company.

Current wording

We anticipate that our general and administrative expenses will continue to increase in the future as we increase our headcount and services to support our continued research activities and development of our drug candidates. We also anticipate that we will continue to incur significant accounting, audit, legal, regulatory, compliance and director and officer insurance costs, as well as investor and public relations expenses associated with operating as a public company.

Previous wording

Other expense, net primarily consists of realized and unrealized gains and losses on foreign currency transactions, state and franchise taxes, and investment management fees.

Current wording

Other income (expense), net primarily consists of realized and unrealized gains and losses on foreign currency transactions, state and franchise taxes, and investment management fees.

Previous wording

a $1.8 million net increase in costs related to ACR-2316, our novel, internally-discovered clinical stage asset. ACR-2316 became our second development program after IND clearance in the third quarter of 2024, upon which we initiated a clinical trial and related activities and broke expenses out separately at that point;

Current wording

a $0.9 million net increase in costs related to ACR-2316, our novel, internally-discovered clinical stage asset. We initiated a clinical trial and related activities in the third quarter of 2024, which has continued to progress through 2025; and

Previous wording

a $2.6 million increase in personnel-related costs, including $0.5 million of changes to stock-based compensation expense, primarily due to an increase in research and development headcount; and

Current wording

a $0.7 million increase in personnel-related costs, including $0.2 million of changes to stock-based compensation expense, primarily due to higher annual salaries over time.

Previous wording

Total other income, net was $1.6 million for the three months ended June 30, 2025, compared to total other income, net of $2.6 million for the three months ended June 30, 2024. The change of $1.0 million is primarily attributable to a decrease in interest income and accretion earned on our investments.

Current wording

Total other income, net was $1.5 million for the three months ended September 30, 2025, compared to total other income, net of $2.7 million for the three months ended September 30, 2024. The change of $1.2 million is primarily attributable to a decrease in interest income and accretion earned on our investments.

Previous wording

General and administrative expenses were $6.5 million for the three months ended June 30, 2025, compared to $6.4 million for the three months ended June 30, 2024. The increase of $0.1 million was primarily due to an increase in payroll and employee-related expenses (including stock-based compensation), partially offset by a decrease in professional fees.

Current wording

Research and development expenses were $45.2 million for the nine months ended September 30, 2025, compared to $45.4 million for the nine months ended September 30, 2024. The decrease of $0.1 million was primarily due to:

Previous wording

a $2.9 million net increase in costs related to ACR-2316, our novel, internally-discovered clinical stage asset. ACR-2316 became our second development program after IND clearance in the third quarter of 2024, upon which we initiated a clinical trial and related activities and broke expenses out separately at that point;

Current wording

a $3.8 million net increase in costs related to ACR-2316, our novel, internally-discovered clinical stage asset. We initiated a clinical trial and related activities in the third quarter of 2024, which has continued to progress through 2025;

Previous wording

a $1.9 million net decrease in costs related to preclinical drug discovery activities progression, which prior to ACR-2316 being granted IND clearance in the third quarter of 2024, had included ACR-2316 and in 2025 is significantly comprised of investment in our preclinical cell cycle program with an undisclosed target;

Current wording

a $1.8 million net decrease in costs related to preclinical drug discovery activities progression, which prior to ACR-2316 initiation in the third quarter of 2024, had included ACR-2316 and in 2025 is significantly comprised of investment in our preclinical cell cycle program with an undisclosed target;

Previous wording

a $1.1 million increase in personnel-related costs, including $0.2 million of changes to stock-based compensation expense, primarily due to an increase in research and development headcount; and

Current wording

a $3.3 million increase in personnel-related costs, including $0.7 million of changes to stock-based compensation expense, primarily due to an increase in research and development headcount and higher annual salaries over time; and

Previous wording

a $0.4 million increase in facilities, supplies and other expenses, primarily driven by an increase in headcount and related research activities.

Current wording

a $1.0 million increase in facilities, supplies and other expenses, primarily driven by an increase in headcount and related research activities.

Previous wording

Total other income, net was $3.6 million for the six months ended June 30, 2025, compared to total other income, net of $3.8 million for the six months ended June 30, 2024. The change of $0.2 million is primarily attributable to a decrease in interest income and accretion earned on our investments.

Current wording

Total other income, net was $5.1 million for the nine months ended September 30, 2025, compared to total other income, net of $6.5 million for the nine months ended September 30, 2024. The change of $1.4 million is primarily attributable to a decrease in interest income and accretion earned on our investments.

Previous wording

Since our inception, we have not recognized any revenue and have incurred significant losses in each period and on an aggregate basis. We have not yet commercialized any drug candidates, and we do not expect to generate revenue from sales of any drug candidates or from other sources for several years, if at all. As of June 30, 2025, we had $147.6 million in cash, cash equivalents and investments, and we had an accumulated deficit of $237.7 million. We have funded our operations primarily with proceeds from the sales of shares of our convertible preferred stock, the issuance of convertible notes, our IPO and concurrent private placement, and our April 2024 Private Placement. We believe that our existing cash, cash equivalents and investments of $147.6 million as of June 30, 2025, will enable us to fund our operating expenses and capital expenditure requirements into the second quarter of 2027.

Current wording

Since our inception, we have not recognized any revenue and have incurred significant losses in each period and on an aggregate basis. We have not yet commercialized any drug candidates, and we do not expect to generate revenue from sales of any drug candidates or from other sources for several years, if at all. As of September 30, 2025, we had $134.4 million in cash, cash equivalents and investments, and we had an accumulated deficit of $255.9 million. We have funded our operations primarily with proceeds from the sales of shares of our convertible preferred stock, the issuance of convertible notes, our IPO and concurrent private placement, and our April 2024 Private Placement. We believe that our existing cash, cash equivalents and investments of $134.4 million as of September 30, 2025, will enable us to fund our operating expenses and capital expenditure requirements into the second quarter of 2027.

Previous wording

Net cash used in operating activities was $36.1 million for the six months ended June 30, 2025, compared to net cash used in operating activities of $31.0 million for the six months ended June 30, 2024. The increase in net cash used in operating activities of $5.1 million was primarily driven by an increase in net loss of $5.4 million, partially offset by a $0.8 million increase in non-cash stock-based compensation expense.

Current wording

Net cash used in operating activities was $48.4 million for the nine months ended September 30, 2025, compared to net cash used in operating activities of $48.3 million for the nine months ended September 30, 2024. The increase in net cash used in operating activities of $0.1 million was primarily driven by an increase in net loss of $1.2 million, partially offset by a $1.0 million increase in non-cash stock-based compensation expense.

Previous wording

Net cash provided by investing activities was $38.7 million for the six months ended June 30, 2025, resulting from $74.5 million in proceeds from maturities of investments, offset by purchases of investments of $35.3 million and purchases of property and equipment of $0.6 million.

Current wording

Net cash provided by investing activities was $44.6 million for the nine months ended September 30, 2025, resulting from $114.5 million in proceeds from maturities of investments, offset by purchases of investments of $68.5 million and purchases of property and equipment of $1.5 million.

Previous wording

Net cash used in investing activities was $82.2 million for the six months ended June 30, 2024, resulting from purchases of investments of $163.2 million and purchases of property and equipment of $1.0 million, offset by $81.9 million in proceeds from maturities of investments.

Current wording

Net cash used in investing activities was $66.2 million for the nine months ended September 30, 2024, resulting from purchases of investments of $168.2 million and purchases of property and equipment of $1.9 million, offset by $103.9 million in proceeds from maturities of investments.

Previous wording

Net cash used in financing activities was $0.4 million for the six months ended June 30, 2025, primarily resulting from $0.4 million of payments for tax withholdings related to the vesting of restricted stock units.

Current wording

Net cash used in financing activities was $0.6 million for the nine months ended September 30, 2025, primarily resulting from $0.6 million of payments for tax withholdings related to the vesting of restricted stock units.

Previous wording

Net cash provided by financing activities was $123.2 million for the six months ended June 30, 2024, resulting from $130.0 million in proceeds from the April 2024 Private Placement and $0.1 million in proceeds from the exercise of stock options, offset by $0.7 million of payments for tax withholdings related to the vesting of restricted stock units and $6.2 million of payments of offering costs.

Current wording

Net cash provided by financing activities was $121.7 million for the nine months ended September 30, 2024, resulting from $130.0 million in proceeds from the April 2024 Private Placement and $0.1 million in proceeds from the exercise of stock options, offset by $1.9 million of payments for tax withholdings related to the vesting of restricted stock units and $6.5 million of payments of offering costs.

Previous wording

As of June 30, 2025, our cash, cash equivalents and investments were $147.6 million. We believe that our existing cash, cash equivalents and investments as of June 30, 2025, will enable us to fund our operating expenses and capital expenditure requirements into the second quarter of 2027. We have based this estimate on assumptions that may prove to be wrong, and we could expend our capital resources sooner than we expect.

Current wording

As of September 30, 2025, our cash, cash equivalents and investments were $134.4 million. We believe that our existing cash, cash equivalents and investments as of September 30, 2025, will enable us to fund our operating expenses and capital expenditure requirements into the second quarter of 2027. We have based this estimate on assumptions that may prove to be wrong, and we could expend our capital resources sooner than we expect.

Previous wording

the cash requirements of any future acquisitions or discovery of drug candidates;

Current wording

the cash requirements of any future in-licenses, acquisitions or discovery of drug candidates;

Previous wording

Except as discussed in Note 12 to our unaudited condensed consolidated financial statements appearing elsewhere in this Quarterly Report, during the six months ended June 30, 2025, there were no material changes to our contractual obligations and commitments from those described in our Annual Report on Form 10-K for the year ended December 31, 2024, which was filed with the SEC on March 27, 2025.

Current wording

Except as discussed in Note 12 to our unaudited condensed consolidated financial statements appearing elsewhere in this Quarterly Report, during the nine months ended September 30, 2025, there were no material changes to our contractual obligations and commitments from those described in our Annual Report on Form 10-K for the year ended December 31, 2024, which was filed with the SEC on March 27, 2025.