Good afternoon, ladies and gentlemen, and welcome to Cullinan Oncology's, CLN-081 Clinical and Regulatory Update conference call. As a reminder, this call is being recorded. Earlier today, the company issued a press release providing a clinical and regulatory update, on its CLN-081 program. This press release, along with a slide deck that you may find helpful while you listen to this call, are available on the events section, of Cullinan's investor relations website at investors.cullinanoncology.com. It is now my pleasure to turn the call over to Chad Messer, Vice President of Investor Relations at Cullinan Oncology.
Good morning, everyone, and thank you all for joining us for our update on the CLN-081 program. My name is Chad Messer, and I'm the Vice President of Investor Relations at Cullinan Oncology. Before we begin, I would like to remind you all of the safe harbor provisions outlined on slide two. During today's presentation, management will be making certain forward-looking statements which are based on current information, assumptions, and expectations that are subject to change, and involve a number of risks and uncertainties, which may cause actual results to differ materially from those contained in such forward-looking statements. These risks are described more fully in the company's filings made with the Securities and Exchange Commission, including our annual report on Form 10-K. You are cautioned not to place any undue reliance on these forward-looking statements, and we disclaim any obligation to update such statements.
In addition, this call contains time-sensitive information, accurate only as of the date of the live broadcast, March 28, 2022. Cullinan undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this call. As shown on slide three, joining me on the call today are Nadim Ahmed, Cullinan's Chief Executive Officer, Dr. Jeff Jones, Chief Medical Officer, Dr. Leigh Zawel, Chief Scientific Officer of Small Molecules, and Jeff Trigilio, Chief Financial Officer. It is my pleasure now to turn the call over to Cullinan CEO, Nadim Ahmed. Nadim.
Thank you, Chad. Good morning, everyone, and welcome to our update call on the CLN-081 program. Let me first start out by reviewing the significant recent progress across our portfolio on slide four. In December, we initiated dosing in the first-in-human clinical trials of both CLN-049 and CLN-619. As a reminder, CLN-049, is our bispecific antibody targeting FLT3, in relapsed refractory AML patients. CLN-619 is our novel antibody targeting the MICA, MICB pathway and has pan-cancer potential. We now have three highly differentiated programs in the clinic. Earlier this month, we had a manuscript with the full preclinical characterization of CLN-049, published in the Journal for ImmunoTherapy of Cancer.
We also recently announced five abstracts from our pipeline accepted, as poster presentation at the upcoming AACR meeting, again demonstrating the breadth and depth of our oncology pipeline. At the same time, as our pipeline was advancing, we also added an eighth program to our portfolio through a new collaboration with Mount Sinai, where we're advancing a novel protein degrader program targeting HPK1, a key regulator of immune cell activation and a high-priority target in the immuno-oncology space. Let me now turn to our lead program, CLN-081, which is the focus of today's call. As you remember, in December, we provided a clinical update from our ongoing phase I/IIa trial, where CLN-081 showed a high response rate, impressive durability, and favorable safety and tolerability, all supporting its differentiated clinical profile.
In January, we were very pleased to announce that CLN-081 had received Breakthrough Therapy Designation from the FDA. On today's call, our recently appointed Chief Medical Officer, Dr. Jeff Jones, will provide both a clinical and regulatory update on the program. We're excited Jeff joined Cullinan Oncology from Bristol Myers Squibb, where he held a range of leadership roles in oncology clinical development. Jeff.
Thanks, Nadim. It's a great time to join Cullinan, and I'm excited to help the team advance the company's broad and deep pipeline of oncology programs. Today, however, I'll share clinical and regulatory updates from our lead program, CLN-081, an orally available irreversible epidermal growth factor receptor inhibitor that selectively targets cells expressing EGFR exon 20 insertion mutations, while relatively sparing cells expressing wild-type EGFR. We are currently evaluating 081 in a phase I/IIa trial in patients with non-small cell lung cancer harboring EGFR exon 20 insertion mutations, whose disease has progressed on or following prior therapy.
On slide five, you can see that we have evaluated doses of CLN-081 ranging from 30 to 150 milligrams BID, and that we expanded enrollment at the 65, 100, and 150-milligram dose levels. We have now enrolled a total of 39 patients at the 100 milligram dose level, which includes the original protocol maximum of 36 patients, plus an additional three patients that were reassigned following our decision to discontinue enrollment at 150 milligrams based on an assessment of the overall clinical profile observed at that dose after 11 patients had been treated. Finally, at the bottom of this slide, you can see that the program has a broad geographic footprint, enrolling patients at U.S. and European sites as well as Asia Pacific. Slide six provides an efficacy update.
When we last shared data in December 2021, we had observed 14 confirmed responses among 36 response evaluable patients treated at 100 mg, yielding a 39% confirmed response rate. Now, including the three additional patients, two of whom achieved a confirmed response, the number of confirmed responses has increased to 16 of 39 patients, and the confirmed overall response rate now stands at 41%. As shown here, almost every patient treated at 100 mg derived some degree of clinical benefit. 97% achieved a best response of partial response or stable disease. Equally important, the responses appeared durable. We have observed an estimated median duration of response that was greater than 15 months, among patients enrolled in the phase I cohort of the 100 mg dose level. In contrast, efficacy has appeared inferior at the 150 mg dose.
Patients treated at that dose achieved a lower 27% confirmed overall response rate, and an estimated median duration of response of only seven months. Slide seven summarizes safety observations at the 100 and 150 mg dose levels, as well as the total for all patients. As we reported back in December, we have observed a favorable safety and tolerability profile at 100 mg. To date, no patients have experienced grade three or higher treatment-related diarrhea or rash at that dose. Events have been manageable with conventional supportive care, and we have not implemented systematic GI prophylaxis for diarrhea management. On the other hand, safety and tolerability appear inferior among patients treated at 150 mg. Adverse events at that dose level have included treatment-related grade three or higher diarrhea, rash, and transaminitis.
A notable increase in rates of dose reduction and dose discontinuation, among patients treated at this dose likewise compares unfavorably to the experience at 100 mg, which could adversely impact therapeutic intensity and persistence. Coupled with inferior efficacy, these observations informed our decision to discontinue further enrollment at 150 milligrams. Overall, we're encouraged to see 081's clinical profile at 100 milligrams strengthen in a growing number of patients. This is a heavily pretreated patient population. 66% of the patients in our trial were progressing to their third or greater line of therapy. Nearly 40% had received prior TKI and 50% prior immunotherapy. We are now observing a response rate of 41%, which is at the high end of other clinically or commercially available EGFR exon 20 agents.
Just as important for patients, we are encouraged by a favorable toxicity profile and durability of response. We look forward to sharing additional insights into the data at upcoming medical conferences. Let's turn now to a regulatory update on slide eight. Cullinan has been engaged in productive discussions with FDA. CLN-081's recent Breakthrough Therapy Designation is facilitating these discussions and reflects the agency's interest in our program. We believe that we are well-positioned to continue advancing 081 toward a pivotal second-line study in the second half of 2022. Thus far, 081 has only been administered under fasting conditions. In that setting, the data we reviewed earlier showed that 100 milligrams emerged as the dose level with the best efficacy and safety profile. Under the same fasted conditions, 150 milligrams was not well tolerated.
27% of patients experienced grade 3 EGFR-associated toxicity, such as rash and diarrhea. 27% of patients had dose reductions, and 18% of patients had dose discontinuations. Under Project Optimus, an initiative undertaken by the FDA Oncology Center of Excellence, the agency aims to reform dose optimization and dose selection, in the development of new oncology drugs such as CLN-081. Ultimately, Project Optimus is intended to enable drug developers to select doses that best balance the efficacy and safety of a therapeutic agent. Consistent with this initiative, and after reviewing safety and efficacy data across the dose range, FDA has encouraged us to explore whether food intake can mitigate the toxicities observed at the 150 mg dose level, prior to the initiation of a pivotal study.
Based on this feedback from FDA, we plan to conduct a small food effect study at the 150 milligram dose designed to evaluate the potential impact of food on exposure and other pharmacokinetic parameters of CLN-081. The study will enroll up to 20 cancer patients, in a randomized single dose two-way crossover design. The FDA has endorsed this plan, and we're committed to completing this food effect study as expeditiously as possible. The food effect study is designed to enable a seamless transition to a pivotal second line study, which we expect to initiate in the second half of this year. With that, I'll close and turn the call back over to Nadim.
Thanks, Jeff. I'll now summarize our clinical and regulatory progress on slide nine. As we review today, CLN-081 continues to show a differentiated clinical profile, relative to other EGFR exon 20 agents. The latest data at the 100 mg BID dose, demonstrate a high response rate above 40%, in a larger number of patients. In terms of quality of response, we saw promising response durability, and a favorable safety and tolerability profile as we previously reported in December. On the regulatory front, we're very grateful for the productive engagement with the FDA, and we look forward to advancing expeditiously to a registrational study. The Breakthrough Therapy Designation for CLN-081 underscores its differentiated clinical profile and the continued opportunity for accelerated approval.
In terms of next steps, we plan to execute the agreed-upon small 150 mg food effect study expeditiously, with a seamless transition to a second-line pivotal study in the second half of 2022. At the same time, we also plan to expand CLN-081 development into the front-line setting, where even more patients can potentially benefit from this novel treatment. In closing, we're encouraged by our clinical and regulatory progress of CLN-081, and remain excited about the potential opportunity we have to improve the standard of care for non-small cell lung cancer patients, harboring EGFR exon 20 insertion mutations.
This concludes today's conference call. Thank you for participating. You may now disconnect.