Q3 2024 CytomX Therapeutics Inc Earnings Call

In This Article:

Participants

Chris Ogden; Senior Vice President - Finance and Accounting; CytomX Therapeutics Inc

Sean McCarthy; President, Chief Executive Officer, Director; CytomX Therapeutics Inc

Joseph Catanzaro; Analyst; Piper Sandler Companies

Etzer Darout; Analyst; BMO Capital Markets

Anupam Rama; Analyst; JP Morgan

Amit Dayal; Analyst; H.C. Wainwright & Co.

Presentation

Operator

Good afternoon, everyone. Thank you for standing by. Welcome to CytomX Therapeutics third quarter, 2024 Financial results call. Please be advised that today's call is being recorded.
I would now like to hand the call over to your host for today. Chris Ogden CytomX, Chief Financial Officer. Please go ahead.

Chris Ogden

Thank you. Good afternoon and thank you for joining us.
Before we begin. I would like to remind everyone that during this call we will be making forward-looking statements because forward-looking statements relate to the future.
They are subject to inherent uncertainties and risks that are difficult to predict and many of which are outside our control.
Important risks and uncertainties are set forth in our most recent public filings with the SEC at sec.gov we do not take no obligation to update any forward-looking statements whether as a result of new information, future developments or otherwise.
Earlier this afternoon, we issued a press release that includes a summary of our third quarter, 2024 financial results and highlights recent progress at atomic.
We encourage everyone to read today's press release and the associated materials which have been filed with the SEC. Additionally, the press release recording of this call and our sec filings can be found under the investors and news section of our website.
With me on the call today is Dr Sean A. McCarthy CytomX is Chief Executive Officer and Chairman Sean will provide an update on our pipeline and company progress. Before I walk through the financials for the third quarter, we will then conclude with a Q&A session with that. I will now turn the call over to Sean.

Sean McCarthy

Thanks Chris and good afternoon, everyone.
As always, we are very pleased to be here today to provide an update on CytomX progress as we advance towards our vision of transforming lives with safer, more effective therapies.
Since our inception and the creation of the PROBODY therapeutic platform. We have been leaders in the field of masked conditionally activated biologics and our team has been working tirelessly to address areas of oncology with high unmet need, leveraging our multi-modality PROBODY platform.
We have more than 15 active discovery and development programs across our internal and partnered research pipeline with 3 of these programs currently in phase 1 physical development CX-904 PROBODY T-cell engager targeted to EGFR and CD-3, CX-2051, an EpCAM directed PROBODY antibody drug conjugate and also CX-801 our PROBODY interferon Alpha-2b.
Each of these programs really stands on the shoulders of our broad platform and clinical experience to date with mass therapeutics. And we continue to push boundaries. In our quest to make the biggest difference we can for cancer patients.
The site services pipeline is poised to deliver multiple clinical readouts in 2025 that will inform next steps for later phase clinical development and create significant value for shareholders.
Now, moving to our pipeline updates for the quarter, I will start with our work in the T-cell engager space.
The field of T-cell engagers in solid tumors has seen meaningful advances over the past 1 to 2 years but there remains a scarcity of really good tumor targets for conventional unmasked T-cell engagers because of target expression in normal tissues.
At CytomX, we are applying our PROBODY therapeutic platform to mask T-cell engagers directed against highly expressed solid tumor targets in order to maximize their activity in tumors and minimize systemic toxicities in normal tissues.
We are working on multiple T-cell engager programs including CX-904. Our mast PROBODY T-cell engager targeting EGFR and CD-3, which is partnered with Amgen in a global Co Development alliance.
EGFR is a well validated target in multiple cancer types. Nobody has yet been able to develop a T-cell engager against this target. So, we are breaking new ground with this program.
CX-904 is designed with a single EGFR binding arm and a single CD-3 binding arm and both are masked in a protease dependent manner allowing for tumor activation.
In May, this year, we shared a first look at safety and efficacy for this clinical program. Announcing positive Phase 1A dose escalation data from 35 patients that showed an emerging favorable safety profile and encouraging early signs of single aged anticancer activity at doses up to 10 mg.
Since our May. Data disclosure dose escalation has continued, and we have been focusing enrolment on patients with Pancreatic ductal adenocarcinoma, non-small cell lung cancer, head, and neck squamous cell carcinoma.
We are pleased to report that the 15 mg step dosing cohort has cleared. A maximum tolerated dose has not been reached for step dosing and escalation continues since the escalation is continuing. We do not expect any decision in 2024 regarding initiation of phase 1B, we continue to engage with our partner and gen regarding plans for CX-904. And we look forward to providing additional updates on the program next year, including potential phase one B initiation.
I would like to turn now to CX-2051. Our wholly owned first in class antibody drug conjugate targeting epithelial cell adhesion molecule or EpCAM developing therapies targeting EpCAM has been a goal of cancer research and development since its first identification as a highly expressed colorectal cancer.
More than 40 years ago, EpCAM is a highly attractive drug target due to its high expression in many solid tuber types, including colorectal cancer, non-small cell lung cancer, ovarian cancer, triple negative, breast cancer, and gastric cancers.
EpCAM has been implicated in many aspects of cancer biology, including signal transduction cell proliferation and epithelial mesenchymal transition. And it is particularly highly expressed in colorectal cancer.
In fact, we estimate that more than 90% of CRC patients have high level EpCAM expression.
Furthermore, we know that if EpCAM can, can be engaged successfully and safely, it can lead to tumor responses in patients. As best demonstrated by the anti EpCAM toxin fusion of Auzam moot that elicited a 40% complete response rate in Non muscle invasive bladder cancer because of its systemic toxicity. Though this drug needed to be administered locally.
Similarly, the previously approved transpacific antibody catchy maxim was shown to be effective in the treatment of malignant ascites. But again, had to be locally administered.
Interest in EpCAM continues to be high across the industry. But why has it taken the field so long to develop a successful systemic anti EpCAM cancer therapeutic?
The answer lies in normal tissue expression.
EpCAM expression is in fact, relatively low on most normal tissues compared to its expression on cancer cells, but it does have particularly high expression in the normal gastrointestinal tract.
This became problematic with first generation anti EpCAM antibodies that induced acute pancreatitis.
Second generation approaches such as the EpCAM CD-3, T-cell engager soliom had even more severe toxicity including grade three and higher upper GI inflammatory diarrhea and acute elevation of liver enzymes at sub therapeutic doses.
So how can we unlock the potential of EpCAM with a systemic therapy.
Well, let me list the key properties of CX-2051 that we believe make it a very attractive clinical candidate.
CX-2051 is a masked high affinity anti-antibody incorporating a [protac] cleavable linker that we have validated clinically. In other contexts, the cytotoxic payload cap-59 is a [Tobiis sos] one inhibitor well matched to cancer types where CM is highly expressed including CRC.
The C-59 payload has comparable preclinical antitumor efficacy to Daiichi's dire TAM both as a free payload and in the context of the [acam] binding ADC.
The payload antibody linker in CX 2051 has been optimized for bystander effect, which is believed to be an important contributor to ADC anticancer activity.
Furthermore, we have shown in preclinical models that CX-2051 is equivalent in activity to the unmasked ADC. But it is much better tolerated in terms of [GIOCS] CX-2051 also has shown antitumor activity in atic and resistant colorectal cancer models. A particularly important finding since we anticipate this drug will be used in the post atic anesthetic CytomX's advanced CX-2051 into the clinic in the second quarter of this year. In Metastatic CRC.
Given the very high expression and substantial medical need in CRC, we are focusing dose escalation in this cancer type to initially assess safety, explore initial science of anti-cancer activity and determine optimal dose levels for further evaluation, EpCAM expression levels in the phase 1 study are being assessed retrospectively and are anticipated to be high in the majority of patients.
And while for now, we are focused in CRC to gain initial experience with 2051 we see a broad opportunity to expand into several additional EpCAM positive tumor types. Once we have a preliminary assessment of safety and anti- tumor activity from this initial study.
I am very pleased to report excellent early progress in the phase one study of CX-2051. We are already enrolling the fifth dose escalation cohort just six months into the trial. And we have observed a favorable safety profile to CX-251 to date suggesting that masking is functioning as designed.
It is still relatively early days. But we see this as a very promising start and we remain on track to provide an initial phase 1, an update in the first half of 2025 to hopefully set the stage for broad based development of this drug.
With respect to the long-term opportunity for CX-251 we estimate that there are approximately 300,000 EpCAM positive addressable patients in the United States alone. So, this program represents a potentially transformational value creating opportunity.
Moving now to our third clinical program, CX-801 our masked interferon alpha two B PROBODY cytokine interferon alpha is a well validated molecule that we view as overlooked in the field of oncology. Interferon has established single agent anticancer activity in multiple tumor types. And it has also demonstrated potential as a combination therapy with checkpoint inhibitors.
The powerful ability of infer alpha to both directly kill tumor cells and drive antigen presentation makes it an ideal mechanism for combination with checkpoint inhibition potentially across a wide range of indications.
CX-801 incorporates a dual masking strategy with a peptide mask, blocking the interferon domains and a steric FC mask which are designed to clamp down the activity of systemic interferon and significantly increase the therapeutic window.
Our preclinical data for CX-801 demonstrates synergy with PD one inhibition both in terms of anti- tumor activity and activation of the tumor inflammatory microenvironment.
Moreover, we have also shown in animal models that systemic activity of our mass interferon is significantly reduced and overall tolerability is markedly improved compared to the unmasked side effects.
We are excited to have recently initiated the phase one clinical study for CX-801 having dosed our first patient during the third quarter.
Our initial goal for this program is to markedly improve on the clinical profile for a mass interferon and PD 1 inhibition in melanoma and CX-801 phase one dose escalation will primarily focus in this tumor type initially as monotherapy. Before moving into combination dose escalation with Keytruda, which we have access to through a collaboration supply group with Merck initial phase 18 data for CX-801 is anticipated in the second half of 2025.
So, with that, let me hand things back over to Chris to provide an update on our finances.

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