Carisma Therapeutics Inc (CARM) 2015 Q2 法說會逐字稿

Welcome to Eleven Biotherapeutics second-quarter 2015 financial results conference call.

(Operator Instructions)

This call is being webcast live on the investors and media section of Eleven Biotherapeutics website at ElevenBio.com. This call is the property of Eleven Biotherapeutics and recordings, reproductions or transmission of this call without the express written consent of Eleven Biotherapeutics is strictly prohibited. As a reminder today's call is being recorded.

I would like to introduce Leah Monteiro, Corporate Communications Manager of Eleven Biotherapeutics.

Thank you. Good morning. The press release with our second-quarter 2015 financial results became available at 7:30 a.m. Eastern Time today. It can be found on the investor and media section of our website at ElevenBio.com.

Before we begin I will read Eleven Biotherapeutics Safe Harbor notice regarding forward-looking statements. During today's call we may make forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These may include statements about the future expectations, plans and prospects, clinical development and regulatory timelines, the potential success of our product candidates, financial projections, projections for 2015 and 2016 milestones and upcoming events and presentations.

Actual results may differ materially from those indicated by these statements as a result of various important factors including those discussed in the risk factors sections in our annual report on Form 10-K and other reports filed with the Securities and Exchange Commission. Any forward-looking statements represent our views as of today only and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change.

During today's call Dr. Abbie Celniker, our President and Chief Executive Officer, will discuss recent Company highlights and our product pipeline development progress. Following Abbie, John McCabe, our Senior Vice President of Finance, will review financial results for the second quarter of 2015. For Q&A, Dr. Michael Goldstein, our Chief Medical Officer, will be joining us.

I would now like to turn the call over to Abbie Celniker.

Thank you, Leah, and good morning everyone. Since our last update we continue to progress our pipeline and we will provide you with that update this morning.

We continue our commitment to moving EBI-005 and EBI-031 forward in patients with ocular inflammatory diseases. Yesterday we were pleased to announce that the first patients have been dosed in the first of two planned pivotal Phase 3 studies of EBI-005 in allergic conjunctivitis.

We also plan to initiate the IND enabling toxicology studies with EBI-031 before the end of the year and expect to file the IND in the first half of 2016. We have sufficient capital to continue to invest in these programs.

Because we do not plan to pursue further development of EBI-005 in dry eye disease we are truncating the duration of the ongoing long-term safety study in dry eye subjects. Randomized subjects will be treated for a minimum of three months and subject to an already completed three months of treatment when we decided to truncate the study we will complete six months of treatment.

As a reminder, allergic conjunctivitis is a mechanistically different ocular disease than dry eye disease due to the single central mechanism of allergen stimulation in allergic conjunctivitis, opposed to the many diverse causes of ocular surface inflammation and dry eye disease. Allergic conjunctivitis ranges in clinical severity from relatively mild common forms to more severe forms that can cause impaired vision and even in the most severe cases blindness. Of the approximately 11 million patients we believe seek treatment for allergic conjunctivitis in the United States, we estimate that about half may not be well maintained on the current standard of care.

These are patients that are on the more moderate to severe end of the disease spectrum. Based on our market research, of the 11 million patients approximately 4 million have moderate allergic conjunctivitis and approximately 1.8 million have severe allergic conjunctivitis and often require treatment with steroids that we know can be associated with sight threatening toxicities.

Our pivotal Phase 3 trial in allergic conjunctivitis is designed to continue to evaluate the safety and efficacy of EBI-005 for up to four weeks in patients with moderate to severe allergic conjunctivitis in an environmental setting. Based on our discussions with the FDA and advice we received from the EEMA we believe that a study in the natural allergy environment should help us to rapidly progress into a global registration program.

Approximately 250 patients will be randomized one-to-one to receive treatment with EBI-005 or the vehicle control. These are patients that have failed or experienced an incomplete response to antihistamines and/or mast cell stabilizers and may have required topical steroids.

Our primary endpoint is ocular itching and secondary endpoints include ocular tearing, total nasal symptoms and conjunctival redness. Other endpoints include safety, tolerability and immunogenicity.

Patients will keep diaries of their experience and environmental pollen counts are monitored throughout the study. We've also included an exploratory arm of the study where approximately 60 to 70 subjects who have completed the environmental part of the study will be further evaluated following a series of direct conjunctival allergen challenges or CACs over a period of three days while continuing to receive the study treatment. We look forward to reporting top-line data from this study in the first quarter of 2016 and if the results are favorable we intend to initiate the second Phase 3 trial in the second half of 2016.

In July Dr. Michael Goldstein, our Chief Medical Officer, gave an oral presentation on ocular surface inflammation and the use of EBI-005 in patients with allergic conjunctivitis and dry eye at the International Symposium on Ocular Pharmacology and Therapeutics or ISOP Meeting in Berlin. In May at the Annual Meeting of the Association for Research in Vision and Ophthalmology or ARVO Dr. Goldstein gave an oral presentation entitled comparison of two clinical repeat allergen challenge models to evaluate EBI-005 in the late phase inflammatory response in allergic conjunctivitis. There he described data from a Phase 2 study in subjects with moderate to severe allergic conjunctivitis in which EBI-005 was evaluated in two different clinical models that had been adapted for the late phase inflammatory response which is an area of high unmet need and the target allergic conjunctivitis patient population for EBI-005 that we continue to study in our Phase 3 program. In a poster presentation at ARVO entitled optimized intravitreal IL-6 antagonist for the treatment of diabetic macular edema, 11 researchers described the preclinical data demonstrating that EBI-031 was an optimized for the drug-like properties necessary for an intravitreal IL-6 antagonist including potent blockade of known IL-6 signaling species and pharmacokinetic properties such as extended vitreal retention and rapid systemic clearance.

EBI-031, our most advanced pipeline candidate, a novel IL-6 antibody for the treatment of back of the eye diseases such as diabetic macular edema and uveitis continues to move forward. Based on our pharmacokinetic modeling, we believe that the potency and intravitreal retention of EBI-031 may result in the need for less frequent intravitreal injections relative to the current standard of care therapy.

Diabetic macular edema or DME is characterized by an abnormal accumulation of fluid in the macula which is the portion of the retina that provides the clearest and most detailed vision. The fluid accumulation is due to leakage from blood vessels in the retina. According to the American Diabetes Association, DME is one of the most common causes of vision loss in the US.

Uveitis is a heterogeneous group of ocular conditions that are characterized by inflammation of the middle layer of the eye known as the uvia. We are focused on filing an IND in the first half of 2016 to initiate the clinical development of EBI-031.

Our enthusiasm for EBI-031 comes from the belief that by blocking IL-6 we are targeting one of the most central pathways in treating DME and other forms of macular edema in that IL-6 may drive blood vessel leakage in at least three ways. First, IL-6 up-regulates VEGF production and the blockade of IL-6 has been observed to reduce VEGF levels including observations following the systemic treatment with IL-6 pathway inhibitor tocilizumab in patients with rheumatoid arthritis.

A recent publication in the peer-reviewed journal Cancer Research provides insight into the second in VEGF independent mechanism where it is indicated that IL-6 stimulates defective angiogenesis by antagonizing the Tie2 pathway and thereby destabilizing vessels. Therefore, blocking IL-6 may have a dual action in decreasing vascular leak by blocking VEGF production and maintaining activity.

Additionally blocking IL-6 should diminish general inflammation which we know is upstream of the initiation of vascular leak in diseases such as DME and uveitis. We remain excited about the potential of our novel drug candidate for the treatment of ocular inflammation and look forward to continuing to update you on our progress.

With that I will now turn the call over to John McCain to provide a review of the financial results for the quarter.

Thank you, Abbie, and good morning to all. Earlier this morning we issued a press release detailing our financial results for the second quarter of 2015. I'll review the financial highlights first and then speak to our cash position and our financial guidance.

For the second quarter of 2015 we reported a net loss of approximately $6.9 million compared to a net loss of $8.2 million for the same quarter in 2014. Total revenue for the second quarter of 2015 was approximately $100,000 compared to $800,000 for the same quarter in 2014. Research and development expenses for the second quarter of 2015 were $6.3 million compared to $6.8 million for the same period in 2014, a decrease primarily driven by lower EBI-005 dry eye disease-related development expenses.

G&A expenses for the second quarter of 2015 were $2.2 million compared to $2.1 million for the same period in 2014. We ended this quarter with $53.5 million in cash and cash equivalents. Based on our current operating plans we believe that we have sufficient cash and cash equivalents to fund our operating expenses and debt service obligations into the second half of 2016.

With that we can open up the call for questions. Operator?

(Operator Instructions) Jason Gerberry, Leerink Partners.

Hi, good morning, thanks for taking my questions. Just a couple on the Phase 3 allergic conjunctivitis trial.

Just curious if you can provide any more details just in terms of magnitude of benefit on the ocular itching endpoint that you need to show relative to placebo in order for the study to be successful? And any additional details you're willing to provide on the powering assumptions for the trial? And then also as you compare this to the Phase 2 study as it relates to the CAPT analysis, just curious what are the meaningful distinctions at all?

It looks like treatment duration or assessment period is pretty similar. Is there any issues around rescue medication like steroid and if you can comment at all on the placebo effect that you see in general on this peak patient reported outcome? Thanks.

Thanks, Jason. I will just give a brief overview and then hand it over to Mike to give you the details. I think one of the things that's very clear for us is that vehicle or placebo effect in allergic conjunctivitis is considerably different than that which you usually see in dry eye disease.

So that's a much less of a consideration than in AC than it is typically in dry eye disease. But I will let Mike talk to you about how the trial was designed, the details of what we need to show from a magnitude perspective and our powering assumptions as well as how we think about how the CAPT translates into the study that we're doing now.

Thank you, Abbie. So in terms of the magnitude of benefit that you need to show, you need to show a statistically significant difference between those patients treated with the drug and those patients treated with the vehicle or the primary endpoint.

So in this case the primary endpoint is looking at subject assessment of ocular itching at multiple time points. So you need to show a statistically significant difference for that endpoint.

In terms of the powering assumptions it's been powered to show to for more than 90% for that particular endpoint. And that data comes from the CAPT study as well as other environmental studies that have been done. And if you compare the current design to the previous CAPT as you mentioned it's really a very similar duration study.

We are actually looking at a very similar patient population, and in particular we're looking at those patients who have failed standard of care therapy which is a topical antihistamine/mast cell stabilizer. What is different with this study is that it's an environmental study where patients are assessed in the natural environment as opposed to the Phase 2 design where patients were actually given the direct conjunctival allergen challenge directly onto the eye. However, they are similar in that CAPT model we did it multiple times which was really designed to get to the effect that you would more likely see in the environmental setting.

Finally, as far as your question about rescue therapy it is a short duration study. Rescue therapy is not part of the protocol, it's not allowed in this study. Of course the patients are needing concomitant medications to control their system, we will actually monitor that, but that is not part of the protocol.

Great, just one follow-up. Do you have to reach significant statistical significance on all time points or is this like an area under the curve analysis?

So the FDA would accept an area under the curve analysis. But you would need to show a statistically significant benefit on the majority of the prespecified time points.

Okay, great. Thank you.

All questions have been answered. Dr. Celniker.

Thank you once again for your participation. You may now disconnect and everybody have a wonderful day.

Ladies and gentlemen, this concludes today's conference. Thank you for your participation and have a wonderful day.