UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
Item 2.02 Results of Operations and Financial Condition.
On April 24, 2024, Acrivon Therapeutics, Inc. (the “Company”) disclosed a preliminary cash and cash equivalents and short-term investments balance of approximately $110 million as of March 31, 2024. The Company also disclosed a preliminary pro forma cash and cash equivalents and short-term investments balance of approximately $234 million as of March 31, 2024, after giving effect to the net proceeds of the Company’s private placement previously disclosed on April 9, 2024.
Because the Company’s consolidated financial statements for the three months ended March 31, 2024 have not yet been finalized, the preliminary statement of the Company’s cash and cash equivalents and short-term investments as of March 31, 2024 in this Item 2.02 is subject to change, and the Company’s actual cash and cash equivalents and short-term investments as of March 31, 2024 may differ materially from this preliminary estimate. Accordingly, you should not place undue reliance on this preliminary estimate.
The information in this Item 2.02 shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended (the “Securities Act”), or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 7.01 Regulation FD Disclosure.
On April 24, 2024, the Company is hosting a virtual corporate R&D event from 4:15 p.m. to 5:30 p.m. ET. The agenda will feature presentations by the Company’s leadership team, followed by an interactive Q&A session. In connection with this event, the Company posted to the “Investors & Media” section of the Company’s website at ir.acrivon.com, a corporate presentation providing an update on the Company’s business (the “Corporate Presentation”). In connection with this event, the Company also issued a press release (the “Press Release”).
Copies of the Corporate Presentation and Press Release are attached hereto as Exhibits 99.1 and 99.2, respectively, and are incorporated by reference into this Item 7.01 of this Current Report on Form 8-K.
The information in this Item 7.01, including Exhibits 99.1 and 99.2 attached hereto, shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 8.01 Other Events.
Phase 2b Initial Clinical Data
On April 24, 2024, the Company announced initial clinical data from its ongoing registrational-intent Phase 2b clinical trial of ACR-368 in patients with ovarian or endometrial cancers (n=26; 10 OncoSignature-positive and 16 OncoSignature-negative). The data presented was as of an April 1, 2024 data cut.
A confirmed objective response rate (“ORR”) (per RECIST 1.1) of 50% was observed in the prospective cohort of OncoSignature-positive patients who were efficacy-evaluable. All confirmed responders continued to be on treatment and median duration of response (“DoR”) had not yet been reached.
The data provided initial, prospective validation of the Acrivon Predictive Precision Proteomics (“AP3”)-based ACR-368 OncoSignature assay’s ability to identify ovarian and endometrial patients sensitive to ACR-368 monotherapy in the ongoing clinical trial, with clear segregation of RECIST responders in the OncoSignature-positive (50% confirmed ORR in 10 patients) versus OncoSignature-negative (0% ORR in 16 patients) arms (p-value=0.0038).
In the OncoSignature-negative arm of the trial with ovarian or endometrial cancers, encouraging signs of clinical activity were observed in response to ACR-368 with ultra-low dose gemcitabine at the recommended Phase 2 combination dose, with 8 out of 16 patients having achieved stable disease.
Consistent with past trials, the ACR-368 treatment-related adverse event profile was predominantly reversible and transient with only mechanism-based, hematological adverse events.
Cash and Cash Equivalents and Short-term Investments
As disclosed above under Item 2.02, on April 24, 2024, the Company disclosed a preliminary cash and cash equivalents and short-term investments balance of approximately $110 million as of March 31, 2024. The Company believes that its pro forma cash and cash equivalents and short-term investments of approximately $234 million as of March 31, 2024, after giving effect to the net
proceeds of the Company’s private placement previously disclosed on April 9, 2024, will be sufficient to fund the Company’s operations into the second half of 2026.
Item 9.01 Financial Statements and Exhibits.
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99.1 |
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SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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Acrivon Therapeutics, Inc. |
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Date: |
April 24, 2024 |
By: |
/s/ Rasmus Holm-Jorgensen |
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Rasmus Holm-Jorgensen |
CORPORATE R&D EVENT APRIL 24, 2024 ACRIVON PREDICTIVE PRECISION PROTEOMICS (AP3) OVERCOMING LIMITATIONS OF GENETICS-BASED PRECISION MEDICINE
Forward-looking statements -looking statements Certain information contained in this presentation includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 regarding our future results of operations or financial condition, business strategy and plans and objectives of management for future operations. In some cases, you can identify forward-looking statements because they contain words such as “anticipate,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” or “would” or the negative of these words or other similar terms or expressions. Our forward-looking statements are based primarily on our current expectations and projections about future events and trends that we believe may affect our business, financial condition and results of operations. The outcome of the events described in the forward-looking statements is subject to risks and uncertainties, including the factors described in our filings with the U.S. Securities and Exchange Commission. New risks and uncertainties emerge from time to time, and it is not possible for us to predict all risks and uncertainties that could have an impact on the forward-looking statements contained in this presentation. The results, events, and circumstances reflected in the forward-looking statements may not be achieved or occur, and actual results, events, or circumstances could differ materially from those described in the forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this presentation. We undertake no obligation to update any forward-looking statements or to reflect new information or the occurrence of unanticipated events, except as required by law.
outline Acrivon Therapeutics and AP3 overview 5 minutes Initial ACR-368 Phase 2 trial data 25 minutes AP3-based drug design: Dual WEE1/PKMYT1 inhibitor ACR-2316 and pipeline 20 minutes AP3 Interactome 5 minutes Live Q&A 20 minutes For a comprehensive corporate deck, please visit: https://Acrivon.com
Acrivon Therapeutics – a next-generation precision medicine company Neurological Cancer Inflammatory Fibrosis Drug P Metabolic Acrivon Predictive Precision Proteomics (AP3) Enables an exact match between the disease-driving, dysregulated pathways with a drug’s mechanism of action (Acrivon meaning ≈ exact, accurate) Broadly applicable in R&D (biological SAR, resistance, patient responders); leveraged for internal pipeline DNA RNA Protein Dysregulated Protein Dysregulated Pathways + OncoSignature®
Acrivon Pipeline Anticipated Next Milestone Phase 3 Phase 2 Phase 1 Preclinical ACR-368 (CHK1/CHK2) Single-Arm Trials Based on OncoSignature Prediction Option to Initiate Additional Trials in HPV+ SCC (H&N, Anal, Cervical) and sarcomas IND Filing in Q3 2024 Trial Initiation Q4 2024 Clinical Data 1H 2024 Platinum-Resistant Ovarian Cancer Endometrial Cancer Bladder Cancer OncoSignature-Predicted Monotherapy Sensitive Tumors Future Development Candidates Additional AP3-driven co-crystallography programs ACR-368 Monotherapy Breakthrough Device & Fast Track Designations LDG Combination ACR-368 Monotherapy LDG Combination Notes Registrational intent Phase 2 single arm trials based on predicted sensitivity to ACR-368 monotherapy in OncoSignature-positive patients Exploratory Phase 1b/2 single arm trials of ACR-368 in combination with low dose gemcitabine, or LDG, in OncoSignature-negative patients LDG Combination ACR-368 Monotherapy Fast Track Designation ACR-368 Monotherapy LDG Combination ACR-2316 (WEE1/ PKMYT1) IND-Enabling Studies OncoSignature-Predicted Monotherapy Sensitive Tumors Cell cycle program (undisclosed target) Development Candidate 2025 Discovery
Acrivon Therapeutics – overview Next-generation precision medicine; Foundational team pioneers in phosphoproteomics-based R&D AP3-based prospective patient responder identification Acrivon in-licensed ACR-368 (Prexasertib) a Lilly flagship program (durable single agent activity across solid cancers, genomics insufficient for patient selection) with 3 key objectives Increase ORR in ovarian cancer using ACR-368 OncoSignature Identify and verify robust clinical activity in new indications (AP3 profiling) Validate our AP3 approach on a challenging drug to provide read through to other drugs (internal pipeline or external) Initial data demonstrate POC for these objectives AP3 applied for drug discovery - ACR-2316 and early pipeline AP3 has generated a potent, single agent active WEE1/PKMYT1 development candidate (Biological SAR) Specifically designed for clinical monotherapy development aiming for accelerated pathway ACR-2316 OncoSignature being generated for indication finding prior to clinical development AP3 has enabled streamlined preclinical development and accelerated timelines (IND filing now expected in Q3, 2024) New potential first-in-class cell cycle program for an undisclosed target initiated following the same AP3 approach AP3 interactome Proprietary, integrated, ML-enabled compound profiling data (~50 million datapoints/2 wk) Version 1.1.1 of AP3 interactome completed to be applied for AI-based drug discovery and development
ACR-368 clinical data Initial data from the ACR-368 prospective patient selection Phase 2 clinical trial in gynecological cancers Data cut as of April 1, 2024
AP3 platform: Drug response prediction in individual patients “Disease Pathway-Based Method to Generate Biomarker Panels Tailored to Specific Therapeutics for Individualized Treatments”: EP 2 229 589, issued June 10, 2015; US2017/0067877A9, pending. OncoSignature® is a Registered Trademark: US Reg. No. 5,718,472; Int. Cl. 5, 42. Intl. Reg. 1382289 \ PROPRIETARY WORKFLOW INTEGRATING PROVEN TECHNOLOGIES STEP 1 STEP 2 STEP 3 BIOMARKER IDENTIFICATION THERAPEUTIC PACKAGE Acrivon drug with predictive BM assay PATIENT RESPONDERS Optimal indications and combinations AP3 DRUG PROFILING Resistant Sensitive BIOMARKER VALIDATION HIGH RES PROTEOMICS BY MS CELL LINES, PDX, HUMAN TISSUE CLINICAL SIGNATURE ASSAY 3-6 BIOMARKERS PROSPECTIVE RESPONSE PREDICTION ON PRETREATMENT BIOPSY No benefit Benefit Predicted Non-responder Predicted Responder Patients without biomarkers critical for drug sensitivity efficiently excluded + OncoSignature® CLASS 1 BM CLASS 2 BM CLASS 3 BM AI-DRIVEN
ACR-368 OncoSignature prediction of drug sensitivity: Biomarker quantitation across human Cancer patient samples Predicted Responder Patient with drug target dependency Class 1 BM Class 2 BM Class 3 BM Patient High Predicted Non-Responder Patient with no drug target dependency efficiently excluded Class 1 BM Class 2 BM Class 3 BM Patient Low
Therapeutic bar for High grade platinum-resistant ovarian and endometrial cancer new approvals Platinum-resistant ovarian cancer: ≥2nd line SOC* ~12% ORR, mDoR 3.7 – 5.7 months Mirvetuximab: Post 1-3 prior lines, FRa-high PROC (~35% of patients; ORR ~35%, PFS = 5.6 months) ~85% of patients with PROC do not benefit from mirvetuximab High grade endometrial cancer: ≥3rd line SOC** ~9% ORR, mDoR 3.1 months ACR-368 clinical activity (without patient selection) in past platinum-resistant ovarian trials: ~12% ORR, mDoR >5.6 months (BRCA-mutant and BRCA wild type patients regardless # lines of prior therapy; Lilly-sponsored 46-center, 8-country, N=169 patient study)^ TPP - high grade PROC: ≥25% ORR with CI lower bound >15% TPP - high grade endometrial cancer: ≥20-25% ORR with CI lower bound >15% * Aurelia trial: Pujade-Lauraine E et al, JCO (2014); Corail trial: Gaillard S et al, JCO (2016) ** Ray-Coquard I et al, BJC (2013) ^ Konstantinopoulos P et al, Gyn Oncol. (2022)
ACR-368-201 status – ovarian and endometrial (locked oncosignature thresholds, prospective trial) 12 weeks confirmatory scan on 11/27. PR confirmed (-30.16%). Clario reported SD (-23% and SD (-28%) 28 weeks scan expected on 3/18 21 patients awaiting 8-week scan 13 patients awaiting 8-week scan OncoSignature-positive ACR-368 RP2D (105 mg/m2) Registrational intent Phase 2 OncoSignature-negative ACR-368 RP2D (105 mg/m2) + ULDG RP2D (10 mg/m2) Exploratory Phase 1B/2 Patients who received at least one dose (N = 26) Patients who received at least one dose (N = 41) Patients with at least the 8-wk scan (N = 10) Patients with at least the 8-wk scan (N = 16) Patients currently on study (N = 21) Patients currently on study (N = 28) Data cut as of April 1, 2024 Patients enrolled (N = 31) Patients enrolled (N = 61; incl. 7 to be dosed) OncoSignature-positive rate =34%, consistent with predicted ~35% based on patient tumor sample OncoSignature screening prior to clinical trial
Oncosignature+ gyn patients – tumor shrinkage (Locked thresholds, prospective evaluation per protocol) BOR = Best overall response BOR PD PD SD SD SD PR PR uPR PR PR 105-004 102-010 124-001 166-003 141-002 102-012 120-011 143-002 120-007 143-004 * *Since data cut off, the one unconfirmed PR has been confirmed bringing the total confirmed PRs to 5 Data cut as of April 1, 2024
OncoSignature-positive phase 2 monotherapy GYN summary– prospective data with locked thresholds ^ Agresti-Coull -Ovarian: The 95% CI^ for ORR = (12%, 77%). For reference, ovarian SOC ~12%. -Endometrial: The 95% CI^ for ORR = (23%, 88%). For reference, endometrial SOC ~ 9% Data cut as of April 1, 2024 All 5 confirmed responders on treatment; median DoR not reached
ACR-368 OncoSignature prospectively predicts sensitivity to monotherapy in ongoing phase 2 trial ORR BM+ (ARM 1) ACR-368 monotherapy BM- (ARM 2) ACR-368 + ULDG Patients (N) Ovarian 40% (2/5) 0% (0/11) 16 Endometrial 60% (3/5) 0% (0/5) 10 Combined 50% (5/10) 0% (0/16) 26 Notes: (non-parametric bootstrap simulation and Fisher test BM+ vs BM-) ORR in ovarian all-comer = 12.5%, which is consistent with JTJN study (12%) P value (confirmed PRs) = 0.0038 Data cut as of April 1, 2024
Endometrial cancer is an AP3-predicted tumor type ACR-368 OncoSignature-based indication finding prior to trial entry ACR-368 OncoSignature imaging demonstrates addiction to CHK1/2 DDR axis Confirmation of predicted sensitivity in genetically non-modified PDX models Confirmation of ACR-368 OncoSignature prediction in PDX tumor tissues pretreatment in >1,000 cancer patients treated with ACR-368 in Lilly-sponsored trials, endometrial cancer was not tested
Oncosignature+ (ARM 1) Spider Plots – locked Thresholds Arm 1 – All GYN Subjects Arm 1 – Ovarian Arm 1 – Endometrial Note: mDoR established in past Phase 2 ACR-368 monotherapy RP2D trials (>200 patients) is between 5.6 months to >10 months (Konstantinopoulos et al, Gyn Oncol (2022); Lee et al, Lancet Oncology (2018)) Still on treatment Data cut as of April 1, 2024
Oncosignature-negative summary (GYN indications) – prospective data with locked thresholds Clear ULDG sensitization and activity (see waterfall plot), but no PRs to date with locked thresholds Data cut as of April 1, 2024
oncosignature-negative (arm 2)- best overall response (Locked thresholds, prospective evaluation) RP2D of ULDG = 10 mg/m2 104-026 166-002 152-002 120-008 124-002 104-023 171-001 109-015 119-002 152-001 113-002 104-028 104-027 148-001 153-004 BOR = Best overall response; One PD subject censored for lack of target lesion data points available in EDC BOR PD PD SD PD SD SD PD PD PD PD SD SD SD SD SD Data cut as of April 1, 2024
Treatment-Related Adverse Events by Indication – OncoSignature-positive (Arm 1) Treatment-related AEs in >15% of subjects, locked thresholds; RP2D (ACR-368 105 mg/m2) ARM 1 Endometrial Ovarian Urothelial ALL (Arm 1) N = 7 N = 14 N = 2 N = 23 All Gr 3/4 All Gr 3/4 All Gr 3/4 All Gr 3/4 Anemia 2 (29) 2 (29) 8 (57) 2 (14) 1 (50) 0 (0) 11 (48) 4 (17) Fatigue 2 (29) 1 (14) 3 (21) 0 (0) 1 (50) 0 (0) 6 (26) 1 (4) Nausea 3 (43) 0 (0) 2 (14) 0 (0) 2 (100) 0 (0) 7 (30) 0 (0) Thrombocytopenia 0 (0) 0 (0) 2 (14) 2 (14) 0 (0) 0 (0) 2 (9) 2 (9) Neutropenia 0 (0) 0 (0) 1 (7) 1 (7) 0 (0) 0 (0) 1 (4) 1 (4) Febrile Neutropenia 0 (0) 0 (0) 2 (14) 2 (14) 0 (0) 0 (0) 2 (9) 2 (9) Data represented as number of subjects (% of subjects); Non-QC'd data, as of 8 March 2024 AE profile predominantly heme, consistent with previous monotherapy trials at RP2D
Treatment-Related Adverse Events by Indication – OncoSignature-negative (Arm 2) Treatment-related AEs in >15% of subjects, locked thresholds, RP2D (ACR-368 105 mg/m2; ULDG = 10 mg/m2) ARM 2 Endometrial Ovarian Urothelial ALL (Arm 2, 10 mg/m2 Gem) N = 11 N = 22 N = 5 N = 38 All Gr 3/4 All Gr 3/4 All Gr 3/4 All Gr 3/4 Anemia 2 (18) 2 (18) 10 (45) 3 (14) 3 (60) 1 (20) 15 (39) 6 (16) Fatigue 1 (9) 0 (0) 9 (41) 2 (9) 1 (20) 0 (0) 11 (29) 2 (5) Nausea 1 (9) 0 (0) 6 (27) 0 (0) 1 (20) 0 (0) 8 (21) 0 (0) Thrombocytopenia 2 (18) 1 (9) 3 (14) 2 (9) 4 (60) 2 (40) 9 (24) 5 (13) Neutropenia 0 (0) 0 (0) 5 (23) 5 (23) 3 (60) 3 (60) 8 (21) 8 (21) Febrile Neutropenia 1 (9) 1 (9) 4 (18) 4 (18) 1 (20) 1 (20) 6 (16) 6 (16) Data represented as number of subjects (% of subjects); Non-QC'd data, as of 8 March 2024 AE profile predominantly heme, consistent with previous monotherapy trials at RP2D
ACR-368 Manufacturing Status Registration and validation campaigns complete with release of all batches 21.9 kg of GMP API in stock (enough for >100k doses) Registration campaign complete with all three batches released and yield ~95% Active Pharmaceutical Ingredient Drug Product
AP3-enabled drug discovery AP3-based drug design: ACR-2316, a potential first-in-class, dual WEE1/PKMYT1 inhibitor and pipeline
Streamlined AP3-based biological SAR OPTIMIZATION FOR SINGLE AGENT ACTIVITY OF PRECLINICAL PROGRAMS Peptide clean up Direct DIA analysis Drug treatment Proteolysis P-peptide enrichment Ultra high resolution P-proteomic profiling Week 0 Week 2 Turnaround <2 weeks Quantitative mapping (>35,000 phospho-sites covering >4,500 proteins) Drug-regulated phospho-sites and biological process enrichment Drug-regulated pathway activity mapping and reconstitution P P Proprietary pipe for automated AP3 analyses with actionable results High resolution and throughput MS-based P-proteomics
AP3: TIGHT, HIGH-RESOLUTION DATA WITH DEEP COVERAGE Acrivon proprietary compound data (~50 million data points per experiment); dozens of compounds profiled Miniaturized, high throughput, scalable: <2 weeks turn-around, automated AI computational analyses in 1 day Actionable results: Resistance mechanisms, rational combinations, drug-tailored OncoSignature patient selection QC MS Data Data Clean Up QC Processed Data Volcano Plots Hierarchical Clustering Consensus Sequence Motif Kinase Inference Pathway Enrichment Functional Annotation Network Mapping Biomarkers 35388 p-sites 15733 p-sites
ACR-2316 –uniquely enabled by AP3 to overcome limitations of current wee1 and pkmyt1 inhibitors Zhu et al, J. Med. Chem. (2017) Program goals: Superior single agent activity (AP3) AP3-guided design to overcome WEE1 and PKMYT1 single inhibitor resistance through balanced dual inhibition High selectivity and potency (co-crystallography) Structure-guided design to limit adverse events (AEs) to be on-target, transient, mechanism-based Streamlined clinical development (ACR-2316 OncoSignature) To identify/prioritize sensitive indications prior to clinical start and for drug target engagement-based dose optimization AP3 used for biologically optimal SAR Co-crystallography for drug design and selectivity ACR-2316: Rationally designed WEE1/PKMYT1 development candidate AP3-based SAR from >40 co-crystals (1.5-3.1 Å) of novel WEE1/PKMYT1-selective series 5-20-fold more potent in preclinical models than clinical benchmarks Superior anti-tumor efficacy with complete tumor regression across models High selectivity ensures transient, short-lived, mild AEs Potent WEE1 inhibition, balanced PKMYT1 inhibition, overcomes resistance
ACR-2316 ++++ ++ ++++ ++++ ++++ Adavosertib ++ - ++ +++ ++ Azenosertib ++ - +++ ++ ++ Debio0123 + - ++++ + + Lunresertib - +++ + + + WEE1 cellular drug target engagement PKMYT1 cellular drug target engagement In vivo efficacy Kinome selectivity Relative performance Human tumor cell viability Acr-2316 shows attractive profile in ongoing preclinical studies
Dual wee1/pkmyt1 inhibitor ACR-2316 demonstrates strong potency and selectivity DNA content 100 nM, 24 hour ACR-2316 exerts potent cell cycle effects with pronounced S-G2/M accumulation KinomeScan (468 kinases @ 1mM) DMSO Azenosertib Lunresertib ACR-2316 94% 41% 58% 50% ACR-2316 is highly selective (KinomeScan) WEE1 PKMYT1 WEE1 WEE1 PKMYT1 ACR-2316 Adavosertib Azenosertib Lunresertib ACR-2316 potently inhibits cancer cell viability
Optimized dual inhibitors show desirable pathway effects Activity (NES) -5 0 5 Substrate motif-inferred kinase activities Kinase activity based on proprietary PTM-SEA-based hybrid workflow and analyses Optimized dual WEE1 and PKMYT1 inhibitors affect cell cycle and canonical MAPK pathways in desirable manner ACR-2743 ACR-2316 Benchmark* WEE1 + PKMYT1 Inhibitors in combination *Clinical-stage selective WEE1 and PKMYT1 inhibitors
ACR-2316 potently activates CDK1, regulating >300 CDK1 consensus substrates and driving mitotic catastrophe Unbiased quantitation of ACR-2316-regulated CDK1 substrate p-sites (308) in intact cells based on CDK1 consensus recognition motif (Acrivon proprietary hybrid database approach) across multiple experiments Actionable insight into drivers of mitotic catastrophe and on-target CDK1-driven pathways CDK1 consensus substrates CDK1 consensus substrates CDK1 consensus substrates CDK1 consensus substrates CDK1 consensus substrates DMSO Res. Sens.
ACR-2316 is highly potent across human tumor cell lines and patient-derived ex vivo tumor models Patient-derived ex vivo tumor models Human tumor cell lines Breast Lung Ovarian Prostate Renal Medulloblastoma Glioblastoma
ACR-2316 induces potent cell death compared to benchmark wee1 and pkmyt1 inhibitors CellTox-Green Assay Most Cytotoxic ACR-2316 Adavosertib Azenosertib Debio 0123 Lunresertib
Acr-2316 induces potent caspase 3/7 cleavage compared to benchmark wee1 or pkmyt1 inhibitors Caspase 3/7-Glo Assay ACR-2316 Adavosertib Azenosertib Debio 0123 Lunresertib Highest Caspase Activity
ACR-2316 induces complete tumor regression across models and dosing regimens 5d on/2 d off Model 1 5d on/2 d off Model 2
Expediting ACR-2316 towards clinical monotherapy development A novel, AP3-enabled, internally discovered dual WEE1 / PKMYT1 inhibitor Rational Design Potent anti-tumor activity across human tumor cell lines and in tumor-bearing mice vs benchmarks Superior Profile Optimized via AP3 AP3-enabled design for optimized single agent activity Streamlined Development Aiming for expedited monotherapy development Advancing towards IND in Q3, 2024, FIH in Q4, 2024 OncoSignature test in development for indication finding Dose optimization to be guided by drug target engagement (BM2)
AP3-derived dual potency optimization to overcome wee1 inhibitor resistance: Reciprocal quenching Induced Suppressed Enrichment Score (NES) 500 5 Protein set size Mitotic regulation Cell cycle and cancer DNA homology repair DNA damage responses Sensitive Resistant WEE1i PKMYT1i PKMYT1i WEE1i PUJANA_BRCA1_PCC_NETWORK PUJANA_CHEK2_PCC_NETWORK REACTOME_CELL_CYCLE REACTOME_SEPARATION_OF_SISTER_CHROMATIDS Protein set name EC75 Comprehensive annotation, weighted for protein set size
AP3 reciprocal quenching reveals optimal target potency profile for dual WEE1/PKMYT1 inhibitor PKMYT1i WEE1i PKMYT1i WEE1i Sensitive Resistant HCL, Euclidean 1043 p-sites from 298 proteins 4 -4 Centered log2FC (treated vs. DMSO) Target substrate of ACR-368 Target substrate of PKMYT1i Optimal potency ratio results in significant synergy WEE1i and ACR-368 WEE1i and PKMYT1i dual inhibition synergy Sensitive Resistant Target substrates Target substrates PKMYT1i WEE1i PKMYT1i WEE1i
Data completeness Peptide IDs CV Pearson Correlation PCA Hierarchical Clustering DEPs Volcano Plots ANOVA Hierarchical clustering Consensus Sequence Motif Kinase Inference Pathway Enrichment Network Mapping Biomarkers Filtering Batch effects Normalization Imputation 50,000 phosphosites 20,000 phosphosites Ap3 interactome v.1: Proprietary Interactive Data analysis infrastructure Actionable data across all AP3 experiments accessible for all Acrivon scientists Fully scripted, algorithm-based machine-learning enabled pathway and biomarker analyses
cell cycle regulatory pipeline program (undisclosed target) Target X – an exciting cancer drug target, no/minimal competitor programs, perfectly suited for AP3 platform DepMap data suggest suggest target X is an essential gene for cancer cell viability Strong mechanistic target rationale for role in oncogenesis Highly selective tool compound shows strong anti-tumor efficacy in rodent models Tool compound AP3 profiling supports selectivity New preclinical program leveraging co-crystallography and AP3 infrastructure successfully built for ACR-2316 Tool compound is a selective target X inhibitor (originally believed to be inhibitor for another target) Development candidate 2025
FINANCIAL HIGHLIGHTS – March 31, 2024 PRO-FORMA Cash and marketable securities ~$234M Projected runway into H2’26 Fully Diluted Shares Outstanding ~43.8M Current operating plan, including PIPE Not including additional financing Pro-forma as of Mar-31-2024 Including net proceeds from recent PIPE Pro-forma as of Mar-31-2024 Including shares and pre-funded warrants issued with recent PIPE Note: Unaudited
Key take-aways Initial clinical data (cut-off date April 1, 2024) have demonstrated prospective validation of our AP3 platform and our key objectives 50% confirmed overall response rate observed in patients with OncoSignature-positive gynecological (ovarian and endometrial) cancers Enrichment of ORR in ovarian cancer (40% confirmed ORR) AP3-based prediction of endometrial cancer to be sensitive to ACR-368 now proven with clinical data and confirmed ORR of 60% All 5 confirmed responders still on treatment, with mDoR not yet reached Initial, prospective validation of the AP3-based ACR-368 OncoSignature assay has demonstrated clear segregation of RECIST responders in the OncoSignature-positive versus OncoSignature-negative arms (p-value=0.0038) Streamlined AP3-based drug design - ACR-2316, our internally-discovered dual WEE1/PKMYT1 inhibitor Demonstrated superior single agent activity in preclinical studies compared to clinical benchmarks Accelerated timelines with anticipated IND filing in Q3 and first-in-human in Q4, 2024 Pro-forma cash and marketable securities ~$234M with runway projected to second half of 2026
Infectious, CNS, and other diseases Oncology Fibrotic and inflammatory Autoimmune Cancers with DDR stress Therapeutic areas Therapeutic modalities Small molecule Bifunctional molecule Antibody ADC Oligo/RNA The AP3 Approach is modality and disease agnostic Current focus
Q&A session
Exhibit 99.2
Acrivon Therapeutics Reports Initial Positive Clinical Data for ACR-368 and Pipeline Program Progress Today at Corporate R&D Event
WATERTOWN, Massachusetts, April 24, 2024 – Acrivon Therapeutics, Inc. (“Acrivon” or “Acrivon Therapeutics”) (Nasdaq: ACRV), a clinical stage biopharmaceutical company developing precision oncology medicines that it matches to patients whose tumors are predicted to be sensitive to each specific medicine by utilizing its proprietary proteomics-based patient responder identification platform, Acrivon Predictive Precision Proteomics (AP3), to host a corporate R&D event. The company plans to present initial positive clinical data from the ongoing registrational-intent Phase 2 ACR-368 clinical trials, which showed prospective validation of the proprietary ACR-368 OncoSignature patient selection biomarker test with a 50% confirmed objective response rate (ORR) in patients with ovarian and endometrial cancers. Acrivon is also sharing new preclinical data for ACR-2316, now with accelerated IND filing timelines, as well as actionable findings with the machine learning-enabled AP3 platform.
“Today we present initial clinical data from our ongoing Phase 2 clinical trial which we believe highlights the power of our next generation proteomics-based AP3 precision medicine platform,” said Peter Blume-Jensen, M.D., Ph.D., chief executive officer, president, and founder of Acrivon Therapeutics. “For the first time, we share statistically significant prospective validation of our AP3 patient selection approach via our ACR-368 OncoSignature assay, which demonstrated the ability to effectively identify cancer patients whose tumors are likely to respond to ACR-368 monotherapy treatment. We are extremely gratified to not only confirm the ability to identify and enrich for patient responders with ovarian cancer, but also for patients with endometrial cancer, a new tumor type identified and predicted to be sensitive to ACR-368 by our AP3 platform prior to clinical trial initiation.”
“Today’s R&D event provides us an opportunity to present the compelling preclinical data of our AP3-based, rationally-designed ACR-2316 dual WEE1/PKMYT1 inhibitor,” said Kristina Masson, Ph.D., M.B.A., co-founder and executive vice president of business operations at Acrivon
Therapeutics, Inc. and president and CEO of the company´s research subsidiary Acrivon AB. “We are excited to announce our accelerated timelines for IND filing, now expected in the third quarter with potential clinical study initiation now anticipated in the fourth quarter of this year. We believe this potential first-in-class asset, which is specifically designed for superior single-agent activity as demonstrated in preclinical studies against benchmark inhibitors, has the potential to address significant unmet treatment needs against a broad range of tumors in patients with limited treatment options.”
Company Provides Program and Data Highlights:
A live and recorded webcast of the event will be available through a link on the Events & Presentations page within the investor section of the company’s website at https://ir.acrivon.com/news-events/events-presentations. The webcast will be available for at least 30 days following the event.
About Acrivon Therapeutics
Acrivon is a clinical stage biopharmaceutical company developing precision oncology medicines that it matches to patients whose tumors are predicted to be sensitive to each specific medicine by utilizing Acrivon’s proprietary proteomics-based patient responder identification platform, Acrivon Predictive Precision Proteomics, or AP3. The AP3 platform is engineered to measure compound-specific effects on the entire tumor cell protein signaling network and drug-induced resistance mechanisms in an unbiased manner. These distinctive capabilities enable AP3’s direct application for drug design optimization for monotherapy activity, the identification of rational drug combinations, and the creation of drug-specific proprietary OncoSignature companion diagnostics that are used to identify the patients most likely to benefit from Acrivon’s drug candidates. Acrivon is currently advancing its lead candidate, ACR-368, (also known as prexasertib), a selective small molecule inhibitor targeting CHK1 and CHK2 in a potentially registrational Phase 2 trial across multiple tumor types. The company has received Fast Track designation from the Food and Drug Administration, or FDA, for the investigation of ACR-368 as monotherapy based on OncoSignature-predicted sensitivity in patients with platinum-resistant ovarian or endometrial cancer. Acrivon’s 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 past third-party Phase 2 trials in patients with ovarian cancer treated with ACR-368. The FDA has granted Breakthrough Device designation for the ACR-368 OncoSignature assay for the identification of ovarian cancer patients who may benefit from ACR-368 treatment. In addition to ACR-368, Acrivon is also leveraging its proprietary AP3 precision medicine platform for developing its co-crystallography-driven, internally-discovered preclinical stage pipeline programs. These include ACR-2316, a potent, selective WEE1/PKMYT1 inhibitor designed for superior single-agent activity as demonstrated in preclinical studies against benchmark inhibitors, and a cell cycle program with an undisclosed target.
Forward-Looking Statements
This press release includes certain disclosures that contain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 about us and our industry that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this press release, including statements regarding our future results of operations or financial condition, business strategy and plans and objectives of management for future operations, are forward-looking statements. In some cases, you can identify forward-looking statements because they contain words such as “anticipate,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” or “would” or the negative of these words or other similar terms or expressions. Forward-looking statements are based on Acrivon’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties that are described more fully in the section titled “Risk Factors” in our reports filed with the Securities and Exchange Commission. Forward-looking statements contained in this press release are made as of this date, and Acrivon undertakes no duty to update such information except as required under applicable law.
Investor and Media Contacts:
Adam D. Levy, Ph.D., M.B.A.
alevy@acrivon.com
Alexandra Santos
asantos@wheelhouselsa.com