8:30 am Coffee & Networking

8:50 am Chair’s Opening Remarks

  • Daniel Speidel Managing Director & Co- Founder, Breakpoint Therapeutics

TACKLING DDR INHIBITOR TOXICITY THROUGH DOSE SCHEDULING & OPTIMIZING TREATMENT PLANS

9:00 am Prioritizing Patient Selection for Combination Studies to Optimize Treatments

  • Oren Gilad Chief Operating Officer, Aprea Theraputics

Synopsis

• Calibrate the value of personalized treatments for heterogeneous patient populations

• Refine patient selection beyond only genomic screening to consider disease progression and metastases

• Reflect on accessibility of clinical samples for screening and imaging

9:30 am Roundtable & Feedback Panel Discussion: What Defines Clinical Success for Current & Next-Generation DDR Inhibitors?

Synopsis

• Can DDR inhibitors overcome the challenges other precision oncology therapies have faced?

• Is maintenance and preventing cancer progression enough?

• When should we pursue combination therapies for patients?

10:30 am Morning Break

DISCOVERY TRACK

Overlapping Toxicity & Overlapping Efficacy of Novel DDR Combination Therapies

11:30 am NP1867: A Chemical Probe for Exploring the Role of DNA Mismatch Repair in Human Disease

Synopsis

• MMR-deficient (MMR-d) tumors are eligible for immune checkpoint therapy, irrespective of tumors type, providing substantial clinical benefit; however, not all MMR-d patients respond to CPI therapy and correlation of tumors mutational burden with clinical outcome is controversial

• Small molecule NP1867 potently and selectively binds to the MutLa heterodimer component PMS2 enabling acute and chronic, dose- and time-dependent, MMR inhibition without removal of the target protein

• NP1867, and appropriate controls, reveal that PMS2 binding inhibits DNA Mismatch Repair in cell-based mechanistic and functional assays, elicits COSMIC mutational signatures consistent with MMR-d patient populations, and renders treated tumour cells immunogenic

12:00 pm ATR & ATM Mode of Action & Therapeutic Potential

Synopsis

• Establishing potential therapeutic and toxicity synergies of DDR combination therapies

• A priori determination of potential toxicity though biological rational of combination choice to streamline discovery

• Delivering optimal potency of novel molecules through optimized chemistry for combination

PRECLINICAL & CLINICAL TRACK

Innovating DDR Molecules to Address Unmet Need

11:30 am SGR-2921, A Clinical Stage CDC7 Inhibitor, Enhances DNA Damage, Replication Stress and Apoptosis in AML Tumor Models

Synopsis

• Schrodinger’s physics-based technology facilitated the discovery of highly potent CDC7 inhibitors, including SGR-2921 which demonstrates strong anti-leukemic activity in various preclinical models of AML mediated through mechanisms that exploit DNA damage and ultimately cell death, which are secondary to enhanced replication stress

• Compelling preclinical activity across various molecular genetic contexts of AML and optimization of SGR-2921 dose and schedule support exploring CDC7 inhibition as a new approach for AML and SGR-2921 as a potential combination partner to current standard-of-care agents

• SGR-2921 is currently being explored in a Phase 1 trial of relapsed/refractory AML and MDS including in patients with p53m disease, potentially providing a unique theapeutic option for this underserved population

12:00 pm IDE161, a Potential First-in-Class Clinical Candidate PARG Inhibitor, Selectively Targets DNA Repair Deficient Solid Tumors

Synopsis

• PARG plays a pivotal role in the maintenance of cancer genome stability through resolution of DNA damage and replication stress

• IDE161 is a potent and selective small molecule PARGi with anti-tumor activity in biomarker defined settings and is currently in clinical development as an anti‑cancer therapeutic for patients with advanced or metastatic cancer

• IDE161’s anti-tumor activity is distinct from PARP inhibition

12:30 pm Lunch

MAXIMIZE DDR THERAPEUTIC SUCCESS THROUGH OPTIMIZED CHEMISTRY AND BBB PENETRATION

1:30 pm Unlocking the potential of CHK1: Discovery of BBI-355, the First ecDNADirected Therapy (ecDTx) for the Treatment of Oncogene Amplified Cancers

Synopsis

• Addressing unmet need of oncogene driven cancers

• Development of CHK1 inhibitor to disrupt cell cycle and cell survival in tumors

2:00 pm Drug Distribution Across the Blood-Brain Tumor-Barrier & Maximizing the Efficacy of DDR Inhibitors in GBM

Synopsis

• Define the extent of BBTB disruption in human GBM

• Evaluate the impact on heterogeneous drug delivery across the BBTB on efficacy

• Consider the effects of drug distribution into normal brain on radiation toxicity

2:30 pm Afternoon Break

VENTURING BEYOND ONCOLOGY FOR DDR INHIBITORS

3:30 pm What is Next for DDR Inhibitors Outside Oncology?

Synopsis

• Rethink what disorders could be treated with DDR inhibitors

• Incorporating lessons from oncology and ponder DDR inhibitors for fibrosis

4:00 pm Chair’s Closing Remarks

  • Daniel Speidel Managing Director & Co- Founder, Breakpoint Therapeutics