UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
January 12, 2021
Date of Report (Date of earliest event reported)
Aprea Therapeutics, Inc.
(Exact name of registrant as specified in its charter)
| Delaware | 001-39069 | 84-2246769 |
| (State or other jurisdiction of incorporation) |
(Commission File Number) |
(IRS Employer Identification No.) |
|
535 Boylston Street Boston, Massachusetts (Address of principal executive offices) |
02116 (Zip Code) |
Registrant's telephone number, including area code: (617) 463-9385
(Former name or former address, if changed since last report): Not applicable
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:
| ¨ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ¨ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ¨ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ¨ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading Symbol(s) |
Name of each exchange on which registered | ||
| Common stock, par value $0.001 per share | APRE | NASDAQ Global Select Market |
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 x
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. x
Item 2.02 Results of Operations and Financial Condition
As discussed below, in connection with participation in the 39th Annual J.P. Morgan Healthcare Conference, Aprea Therapeutics, Inc. (the “Company”) updated its corporate presentation to include disclosure that the Company had $89.0 million of cash and cash equivalents (unaudited) as of December 31, 2020.
Because the Company’s consolidated financial statements for the year ended December 31, 2020 have not yet been finalized or audited, the preliminary statement of the Company’s cash and cash equivalents as of December 31, 2020 in this Item 2.02 is subject to change, and the Company’s actual cash and cash equivalents as of December 31, 2020 may differ materially from this preliminary estimate. Accordingly, you should not place undue reliance on this preliminary estimate.
Item 7.01 Regulation FD Disclosure
Beginning on January 12, 2021, the Company will participate in the 39th Annual J.P. Morgan Healthcare Conference. The Company has updated its corporate presentation that it intends to use in connection with its presentation on Tuesday January 12, 2020 at 2:50 p.m. Eastern Time in meetings with investors. The updates primarily include updates on the Company’s ongoing and planned clinical trials and disclosure regarding the Company’s cash and cash equivalents as of December 31, 2020.
A copy of the Company’s corporate presentation is attached hereto as Exhibit 99.1 and is hereby incorporated by reference herein.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits.
|
Exhibit |
Description | |
| 99.1 | Aprea Therapeutics, Inc. Presentation |
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.
| Aprea Therapeutics, Inc. | ||
| Dated: January 12, 2021 | By: | /s/ Christian S. Schade |
| Name: Christian S. Schade | ||
| Title: Chairman and Chief Executive Officer | ||
Exhibit 99.1
J.P. Morgan 39 th Annual Healthcare Conference January 2021
Forward - Looking Statements Certain information contained in this presentation includes “forward - looking statements”, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, related to our clinical trials and regulatory submissions. We may, in some cases use terms such as “predicts,” “believes,” “potential,” “con tin ue,” “anticipates,” “estimates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “likely,” “will,” “should” or other words th at convey uncertainty of the future events or outcomes to identify these forward - looking statements. Our forward - looking statements are based on current beliefs and expectations of our management team that involve risks, potential changes in circumstances, assumptions, and uncertainties. Any or all of the forward - looking statements may turn out to be wrong or be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. These forward - looking statements are subject to risks and uncertainties including risks related to the success and timing of our clinical trials or ot her studies and the other risks set forth in our filings with the U.S. Securities and Exchange Commission, including our Quarterl y Report on Form 10 - Q. For all these reasons, actual results and developments could be materially different from those expressed in or implied by our 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 publicly update such forwa rd - looking statements to reflect subsequent events or circumstances. © 2021 Aprea Therapeutics. All Rights Reserved 2
Aprea Therapeutics ▪ The global leader in p53 - targeted therapies for the treatment of cancer ◊ Proof - of - concept and proof - of - principle demonstration of mutant p53 reactivation Presentation Agenda ▪ Update on Phase 3 MDS Clinical Study ▪ Development Pipeline ◊ 1L AML ◊ Post - transplant maintenance in MDS/AML ◊ CLL / MCL ◊ Advanced solid tumors ▪ Financial and Operational Highlights ▪ 2021 Milestones © 2021 Aprea Therapeutics. All Rights Reserved 3
p53: The “Guardian of the Genome” © 2021 Aprea Therapeutics. All Rights Reserved 4 p 53 tumor suppressor The nexus and regulator of key anti - cancer network of signals • Triggers cell cycle arrest and apoptosis in response to DNA damage and other cellular stresses The most frequently mutated gene in human cancers • Mutations in the TP53 gene occur in approximately 50% of tumors • p53 mutations destabilize the protein and lead to protein misfolding Mutations are associated with very poor prognosis • TP53 mutations compromise tumor suppressive function and can promote tumor growth and metastasis
Reactivation of Mutant p53 Across Mutation Types ▪ p53 protein destabilization is a general and direct consequence of mutation ▪ Eprenetapopt MoA is agnostic to specific p53 mutation, capitalizes on principles of protein folding & stability ◊ Activity observed in nearly 100 different p53 mutations in preclinical studies across hot spots and other mutations ◊ Clinical responses recorded in patients spanning more than 80 unique p53 mutations across hot spots and other mutations © 2021 Aprea Therapeutics. All Rights Reserved 5 6723 misfolded mutant p53 cell cycle arrest apoptosis + eprenetapopt reactivated p53 with wild - type structure p53 reactivation
Clinical Development © 2021 Aprea Therapeutics. All Rights Reserved 6
Molecule Indication Preclinical Phase 1 Phase 2 Phase 3 Eprenetapopt (APR - 246) 1L TP53 Mutant MDS 1 1L TP53 Mutant MDS and AML (U.S. study) 2 1L TP53 Mutant MDS and AML (French study) 2 TP53 Mutant MDS and AML Post - Transplant Maintenance 1L and R/R TP53 Mutant AML R/R TP53 Mutant CLL and MCL Advanced Gastric, Bladder, NSCLC APR - 548 1L and R/R TP53 Mutant MDS Execution on Clinical Development © 2021 Aprea Therapeutics. All Rights Reserved 7 1 Trial did not achieve statistical significance in primary endpoint of complete remission; 2 Investigator - initiated trials; 3 azacitidine; 4 venetoclax; 5 venetoclax + rituximab eprenetapopt + aza 3 eprenetapopt + aza eprenetapopt + aza eprenetapopt + aza eprenetapopt + ven 4 and/or aza eprenetapopt + pembrolizumab APR - 548 + aza eprenetapopt + ibrutinib or ven - R 5 Publication pending Publication pending
Phase 3 MDS Review © 2021 Aprea Therapeutics. All Rights Reserved 8
Randomized Phase 3 Trial in 1L TP53 Mutant MDS Trial design © 2021 Aprea Therapeutics. All Rights Reserved 9 1:1 Randomization Eprenetapopt + AZA AZA Patients • N = 154 • At least one TP53 mutation • Int/High/Very High IPSS - R • ECOG performance status of 0, 1 or 2 • De novo and secondary MDS eligible • HMA naïve Trial Endpoints • Primary: CR rate • Secondary: OS, ORR DoR , DoCR , PFS, LFS, HSCT rate, TI rate Powered at 90% to detect 2 - sided alpha of 0.05 - based on initial assumptions of 50% CR in eprenetapopt + AZA arm vs. 25% CR in AZA arm Same eligibility criteria, treatment doses and sites as Phase 1b/2 trials
Recap of Results from Phase 3 Trial in TP53 Mutant MDS ▪ Primary data cut (LPI + 6 months) ◊ Failed to meet CR primary endpoint in ITT population ◊ 33.3% in eprenetapopt + AZA arm vs. 22.4% in AZA alone arm (P = 0.13) ◊ Primary endpoint did not reach statistical significance ◊ CR rate was 53% higher in eprenetapopt + AZA arm ◊ 24 patients on study treatment: 14 patients on eprenetapopt + AZA, 10 patients on AZA ◊ Secondary endpoints ◊ ORR and duration of responses appear to favor eprenetapopt + AZA arm but are not significantly different from AZA alone ◊ Median OS was similar between arms ◊ Preliminary analysis of clinical subsets based on demographics and disease characteristics (e.g., IPSS - R, bone marrow blast %, p rior therapy) has not identified a group significantly favoring the eprenetapopt + AZA arm ◊ Combination of eprenetapopt + AZA appeared well - tolerated ◊ Adverse event profile similar to Phase 2 US and French trials ◊ Ongoing and future analyses ◊ Mutation and pharmacokinetic data analyses ◊ Other potential ad hoc analyses ◊ Subsequent analyses to be performed at LPI + 9 months ◊ Anticipate discussion of results with FDA in 1H 2021 ◊ Anticipate presentation of results at an upcoming scientific conference © 2021 Aprea Therapeutics. All Rights Reserved 10
Pipeline © 2021 Aprea Therapeutics. All Rights Reserved 11
TP53 Mutant AML is a Major Unmet Medical Need with Limited Treatment Options © 2021 Aprea Therapeutics. All Rights Reserved 12 Global Data, “Acute Myeloid Leukemia Forecast to 2029” 20 - 30% TP53 mutant 45,000 in 2019 in US/EU5/JP 0 - 20% complete remission (CR) ~6 months overall survival (OS) Incidence TP53 mutation is common Prognosis with available therapies
1L TP53 Mutant AML Trial ▪ Current Eprenetapopt Data and Therapeutic Benchmark ▪ Phase 1/2 AML Trial Plan © 2021 Aprea Therapeutics. All Rights Reserved 13 1 Phase 1/2 AML Trial as of December 31, 2020; 2 Dinardo et al, EHA 2020; Dinardo et al, N Engl J Med 2020; 383:617 - 629; 3 Patients who have undergone repeat bone marrow biopsy; 4 Aldoss et al, Br J Hematol , 2019, Dinardo et al, Blood, 2020, have described CR rates of 23% and 22%, respectively, in AML patients receiving Ven - Aza eprenetapopt + AZA + venetoclax (N = 6) eprenetapopt + AZA + venetoclax (N = 20 / 33 enrolled) eprenetapopt + AZA (N = TBD) Best regimen (N ≤ 50) · completion of enrollment · potential BTD application File for accelerated approval based on positive data 3Q 2020 Lead - in Phase Expansion Phase 1H 2021 1H 2022 1Q 2020 No DLTs observed in lead - in phase Phase 1/2 AML Trial 1 ( Eprenetapopt + Ven + AZA) Benchmark 2 Evaluable 3 AML patients, n 6 (lead - in) + 6 (expansion) 38 (Ven - Aza: VIALE - A) 14 (Aza: VIALE - A) Response rates CR + CRi 58% 55% (Ven - Aza: VIALE - A) 0% (Aza: VIALE - A) CR 25% ? 4 (Ven - Aza: VIALE - A) 0% (Aza: VIALE - A)
Post - Transplant Maintenance Therapy in TP53 Mutant MDS and AML Unmet Need ▪ Allo - HCT is currently the only potentially curative option for TP53 mutant MDS/AML, however only 5 - 10% of patients are able to undergo transplantation ▪ Prognosis remains poor even in patients who undergo transplantation ◊ 30% relapse free survival (RFS) at 1 - year ◊ ~8 mo median OS Development Status ▪ Phase 2 Trial of Post - Transplant Maintenance in TP53 mutant MDS and AML ◊ Eprenetapopt + AZA maintenance up to 12 months ◊ Primary endpoints: relapse - free survival, tolerability ◊ Secondary endpoints: OS, non - relapse mortality, PFS, LFS, GVHD, EFS ◊ Trial fully enrolled with N = 33 ◊ 1 - year RFS primary endpoint readout anticipated 2Q 2021 © 2021 Aprea Therapeutics. All Rights Reserved 14 Lindsley et al, New England J Med, 2017, 536.
Eprenetapopt Combination in R/R Lymphoid Malignancies Unmet Need ▪ There is a lack of effective treatments for R/R TP53 mutant CLL and MCL Rationale ▪ Preclinical data demonstrating synergistic activity of eprenetapopt + venetoclax, eprenetapopt + ibrutinib ▪ Encouraging clinical data in CLL from first - in - human trial with eprenetapopt monotherapy Development Status ▪ Phase 1 Trial in TP53 mutant R/R CLL and MCL ◊ Safety Lead - in ◊ Eprenetapopt + ibrutinib in CLL (N ≈ 28) ◊ Eprenetapopt + venetoclax - rituximab in CLL (N ≈ 28) ◊ Expansion ◊ Eprenetapopt + X in CLL (N ≈ 20) and MCL (N ≈ 40) ◊ First patient anticipated 1Q 2021 ◊ Preliminary tolerability and efficacy data anticipated 2H 2021 © 2021 Aprea Therapeutics. All Rights Reserved 15 Global Data, “Chronic Lymphocytic Leukemia: Opportunity Analysis and Forecasts to 2027”; “B - Cell Non - Hodgkin’s Lymphoma (NHL): Opportunity Analysis and Forecasts to 2027” CLL: ~45,000 annually in US/EU5/JP MCL: ~7,000 annually in US/EU5/JP ~50% TP53 mutant in R/R 0 - 20% complete remission (CR) ≤ 12 months overall survival (OS) Incidence TP53 Mutation Prognosis
Eprenetapopt Combination in Advanced Solid Tumors Unmet Need Rationale ◊ APR - 246 enhances effects of PD - 1 blockade in murine melanoma and colorectal carcinoma models ◊ APR - 246 induces pro - inflammatory tumor microenvironment and activity driven by tumor associated macrophages Development Status ▪ Phase 1/2 Solid Tumor Trial Design ◊ Safety Lead - in ◊ Eprenetapopt + pembrolizumab in advanced solid tumors (N = 6) ◊ Expansion ◊ Advanced gastric (N ≈ 40), bladder (N ≈ 40), and NSCLC (N ≈ 20) ◊ Safety lead - in cohort enrollment complete (N=6) and no DLTs ◊ Expansion cohort enrollment ongoing ◊ Preliminary tolerability and efficacy data anticipated 2H 2021 © 2021 Aprea Therapeutics. All Rights Reserved 16 Global Data, “Gastric Cancer – Epidemiology Forecast to 2024”; “Bladder Cancer: Epidemiology Forecast to 2028”; “Non - Small Cell Lung Cancer: Epidemiology Forecast to 2025”; Ghosh et al, 2019 AACR Annual Meeting, Abstract 4843 Gastric: ~185,000 annually in US/EU5/JP Bladder: ~225,000 annually in US/EU5/JP NSCLC: ~500,000 annually in US/EU5/JP ~50 - 80% TP53 mutant 0 - 10% complete remission (CR) ≤ 12 months overall survival (OS) Incidence TP53 Mutation Prognosis
APR - 548: Next - Generation Oral p53 Reactivator ▪ APR - 548 is converted to MQ, shares a similar mechanism of action to eprenetapopt ◊ High oral bioavailability supportive of oral administration ◊ Greater potency than eprenetapopt in preclinical studies ◊ Faster conversion to MQ may provide for higher intra - tumoral drug levels © 2021 Aprea Therapeutics. All Rights Reserved 17 1 Mice received APR - 548 by twice daily oral administration for three consecutive cycles (five days on treatment, two days off treatment) starting on day 11 post - implant of MDA - MB - 231 breast cancer cells Induction of Apoptosis and Reduction of Cell Proliferation in R248Q p53 mutant myeloid cells 0 10 20 30 40 50 PO 2x47 mg/kg/day PO 2x94 mg/kg/day PO 2x188 mg/kg/day TGI (%) Tumor Growth Inhibition (TGI) in R280K p53 mutant Breast Cancer Xenograft 1 Reduction of Ki67 (proliferation marker) Induction of cleaved caspase - 3 (apoptosis marker)
First - in - Human Clinical Trial of APR - 548 in TP53 Mutant MDS IND and protocol have been accepted by FDA ▪ Overview of FIH Trial ◊ Provides opportunity to collect blood and bone marrow samples to study pharmacodynamics ▪ Status ◊ FPI anticipated Q1 2021 ▪ Following completion of FIH Phase 1, possibility to explore expansion in MDS, AML or other indications © 2021 Aprea Therapeutics. All Rights Reserved 18 Cycle 1 APR - 548 dose escalation monotherapy lead - in phase Cycle 2+ APR - 548 dose escalation + AZA combination therapy
Financial and Operational Highlights ▪ Financial ◊ $89.0 million of cash and cash equivalents (unaudited) at December 31, 2020 ◊ No outstanding debt ◊ Anticipated cash burn for 2021: $30 – 35 million ◊ Existing cash should fund operations into 2023 ◊ Consider strategic alternatives ▪ Operational ◊ 17 full - time employees ◊ Clinical trials designed to efficiently reach preliminary efficacy readouts ◊ Clinical data will drive decisions on further development and strategic options © 2021 Aprea Therapeutics. All Rights Reserved 19
2021 Anticipated Milestones Milestones Timeline Phase 2 MDS / AML post - transplant maintenance Primary endpoint readout 2Q 2021 Phase 1/2 AML Trial Tolerability and efficacy data from cohort expansion 2Q 2021 Phase 1 NHL Trial Preliminary tolerability and efficacy data 2H 2021 Phase 1/2 Solid Tumor I - O Trial Preliminary tolerability and efficacy data 2H 2021 2 nd Generation p53 reactivator, APR - 548 First patient enrolled in Phase 1 trial 1Q 2021 © 2021 Aprea Therapeutics. All Rights Reserved 20