Karen Akinsanya
Analyst · BMO Capital Markets
Thank you, Ramy, and good morning everyone. We are continuing to make important advances on many fronts across our internal pipeline and Portfolio with collaborative programs. We have collaborations with both biotech and large pharmaceutical companies, spanning a broad range of target classes. And in these collaborations, we are leveraging our platform at the same scale we do internally. We believe this level of large-scale deployment enables us to more rapidly identify high-quality development candidates. We expect several collaborative programs to continue to advance in the clinic and new programs to enter the clinic this year. We are excited to begin working with our new partner, Zai Lab, on a program targeting DNA repair vulnerabilities in cancer that we anticipate will be synergistic with PARP inhibitors. Marketed PARP inhibitors have demonstrated efficacy in multiple cancers, but new regimens and combinations that results in durable responses are needed, especially in patients who relapse or become resistant to treatment. We are also continuing to build early-stage clinical experience to support the advancement of our internal program. Today, I will highlight through our three most advanced programs, MALT1, CDC7, and WEE1. We have initiated IND -enabling studies for our development candidate targeting MALT1, and we are working towards the nomination of development candidates for CDC7 and WEE1. Subject to completion of the preclinical data packages, we expect to submit up to 3 IND applications in 2022, with our first submission expected in the first half of next year. Starting with our MALT1 inhibitor program, MALT1 inhibition is gaining increasing attention as a therapeutic strategy to treat certain relapse store resistant B-cell lymphomas and chronic lymphocytic leukemia. The MALT1 enzyme is downstream of BTK in the NF kappa B signaling pathway. And constant activation of NF kappa B is a hallmark of several types of lymphoma. Preclinical data previously presented from our MALT1 program showed potent in vitro inhibition of MALT1 enzymatic activity, and in vivo anti-tumor activity in mouse xenograft models of diffused large B-cell lymphoma. Additionally, in in vivo patient-derived tumor mouse models, our MALT1 inhibitors demonstrated dose-dependent, anti-proliferative effects as monotherapy, and in combination with Ibrutinib and Venetoclax, which are approved BTK and BCL-2 inhibitors, respectively. In the second quarter, we selected a development candidate for this program and have since initiated GLP-tox studies required for IND submission. All our IND enabling activities are on track and we expect to submit the IND and begin Phase 1 studies in patients with hematological malignancies next year. Now, I will turn to CDC7 and WEE1, two programs that target cancer through replication stress and DNA repair mechanisms. CDC7 is thought to be linked to cancer cells' proliferative capacity and ability to bypass normal DNA damage responses. Targeting proteins that play important roles in DNA replication and replication strategy is gaining momentum as a therapeutic approach for cancer. Earlier this year we presented preclinical data from our CDC7 Inhibitor program, which showed the tower compounds are synergistic with several approved and investigational cancer therapies that modulate apoptosis, DNA repair mechanisms, and DNA checkpoints. These compounds significantly inhibited tumor growth in mouse models of both acute myeloid leukemia and colorectal cancer. The data we have generated to date suggests that we have an opportunity to develop a best-in-class inhibitor with a very favorable pharmacokinetic profile. Our other DNA damage repair program targets WEE1, a tyrosine kinase regulator of the G2/M cell cycle checkpoint, which when inhibited, reduces cell viability by inducing apoptosis of cancer cells. WEE1 inhibitors from other companies have shown clinical proof of concept as monotherapy in uterine serous carcinoma. Combinations with chemotherapy, PARP inhibitors, and PD-1 antibodies are being pursued by others in the clinic. We have identified multiple WEE1 inhibitors that are highly selective for WEE1 and shows strong pharmacodynamic responses and anti-tumor activity in vivo. Our molecules also have optimized drug-like properties, including no observable inactivation of CYP3A4, a key liver enzyme. We believe this profile limits the potential for accumulation and the need for dose adjustments with combination products. In summary, we have multiple programs advancing towards the clinic to enable up to 3 IND submissions in 2022. As these programs advance and transition into development, we are initiating new programs. We have began drug discovery on an undisclosed target in immunology and have prioritized several additional program opportunities with human genetic support and emerging pharmacology data in oncology and immunology that we expect to advance this year. We are excited about the progress that we and our collaborators are making, and look forward to updating you on our R&D activities throughout the year. I will now turn the call over to Joel to review our Financial results.