Carisma Therapeutics Inc (CARM) 2014 Q4 法說會逐字稿

Welcome to Eleven Biotherapeutics fourth-quarter and full-year 2014 financial results conference call. At this time all participants are in a listen-only mode. This call is being webcast live on the investors and media section of Eleven's website at IR.ElevenBio.com. This call is the property of Eleven Biotherapeutics and recordings, reproduction or retransmission of this call without the written express consent of Eleven Biotherapeutics is strictly prohibited. As a reminder, today's call is being recorded.

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

Thank you. Good morning. The press release with the Company's fourth-quarter and full-year 2014 financial results became available at 7:30 AM Eastern time today. It can be found on the investors and media section of the Company's website at IR.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 our future expectations, plans and prospects, clinical development and regulatory timelines, the potential success of our product candidates, financial projections, projections for 2015/2016 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 section in our most recent quarterly report on Form 10-Q 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.

These forward-looking statements should be relied upon as representing our views as of any date subsequent to today.

Joining me on the call today is Abbie Celniker, PhD, President and Chief Executive Officer of Eleven Biotherapeutics, who will discuss recent Company highlights and review our pipeline (inaudible) progress. Following Abbie, Greg Perry, Eleven Biotherapeutics Chief Financial and Business Officer, will review the Company's financial results for both the fourth-quarter and full-year 2014 after which we will open the call for Q&A. For Q&A, Dr. Michael Goldstein, Eleven Biotherapeutics 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. 2014 was a tremendous year for us at Eleven. The success we experienced has positioned us to have an exceptional 2015 where we will be focused on multiple Phase 3 studies as well as advancing our early pipeline. Last year we completed enrollment in our OASIS study which was our first pivotal Phase 3 clinical study for our topically administered blocker of IL-1, EBI-005, in patients with dry eye disease.

We also initiated a Phase 3 clinical study in patients with moderate to severe dry eye disease to assess the long-term safety and tolerability of EBI-005 in subjects who are treated for 12 months. In October, we reported the top-line results for our Phase 2 clinical trial of EBI-005 in patients with moderate to severe allergic conjunctivitis. In a modified capped or conjunctival allergen propagation test model, patients treated with EBI-005 showed statistically significant improvements in mean change from baseline in patient-reported ocular itching, ocular tearing and total nasal symptoms when compared to the vehicle control.

Also over the course of the year, we continued to advance our EBI-031 anti-IL-6 program toward an expected IND filing for the indication of diabetic macular edema, or DME, targeted for the end of 2015.

Towards the end of last year, we also completed a financing of $20 million allowing us to further advance all of these exciting programs.

Before turning to our lead Phase 3 trial in dry eye disease, we wanted to discuss allergic conjunctivitis as we promised to update you on that program in early 2015. As we previously described according to a study on the management of seasonal allergic conjunctivitis that was published in 2012 in the peer-reviewed journal Acta Ophthalmologica, allergic conjunctivitis affects 15% to 40% of the US population. Based on our market research we believe that approximately 11 million patients seek medical treatment for allergic conjunctivitis annually.

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. Allergic conjunctivitis is understood to have two phases, an acute early phase and a late inflammatory phase. While the acute phase of allergic conjunctivitis is well treated with currently available topical anti-histamine or mast cell stabilizer, patients who suffer from the late inflammatory phase have more severe allergic conjunctivitis and this represents an area of significant unmet clinical need.

Of the approximately 11 million patients we believe seek treatment for allergic conjunctivitis in the United States, we estimate based on our market research that approximately 4 million have moderate allergic conjunctivitis which has increasing inflammatory involvement and approximately 1.8 million have severe allergic conjunctivitis, which is primarily experienced as the late inflammatory phase and is often not adequately treated with anti-histamines or mast cell stabilizers and as such, may require treatment with steroids which are known to be associated with sight threatening side effects such as intraocular pressure increases which can lead to glaucoma.

Based on the unmet need for patients who experience symptoms driven by this late phase allergic response and showing proof of concept in treating the late phase allergic response in our study using the modified CAPT model, we are excited to communicate that we plan to move forward in this indication. Following a recent meeting with the FDA, we are pleased to announce that we intend to initiate the first of two planned pivotal Phase 3 studies of EBI-005 in allergic conjunctivitis in the second half of this year. These studies will be conducted under conditions of natural environmental allergen exposure similar to how other non-anti-histamine mast cell stabilizers have been developed in the past.

We also believe our data from our Phase 2 study in allergic conjunctivitis further supports the importance of IL-1 blockade in treating ocular surface inflammatory disease. Based in part on our discussions with the FDA and our previous scientific advice from the EMEA, this natural environmental study should allow us to move rapidly into a global registration program.

Moving to dry eye, this is a disease that affects the ocular surface and is characterized by symptoms of dryness, pain, discomfort and irritation. If dry eye disease is left untreated or becomes severe patients may suffer chronic ocular pain and distortion of vision that can significantly reduce their quality of life. Dry eye disease is one of the leading causes of patients' visits to eye care professionals in the United States.

According to Market Scope, a publisher of research and analysis on the ophthalmic market, approximately 68 million people in the United States, European Union, Japan and other developed markets have dry eye disease including approximately 26 million people who suffer from moderate to severe forms of dry eye disease. Approximately 19 million people in the United States have dry eye disease including approximately 7 million people who suffer from the moderate to severe form of dry eye disease.

We look forward to reporting the topline data from our Phase 3 study with EBI-005 in patients with moderate to severe dry eye disease in the second quarter of this year. And assuming favorable results, we will begin a second Phase 3 efficacy study later this year.

We have developed and are validating our commercial manufacturing process and are beginning to invest in prelaunch activities as we focus on the BLA filing by the end of 2016.

We are pleased with our IP position based on being granted a US patent for EBI-005 which contains both composition of matter and method of use claims with a patent life through 2031.

Now looking at our pipelines, EBI-031 is our most advanced preclinical product candidate and is a novel anti-IL-6 antibody for the treatment of back of the eye diseases such as diabetic macular edema and uveitis. Diabetic macular edema or DME is characterized by an abnormal accumulation of fluid in the macula, the portion of the retina that provides the clearest and most detailed vision and it is due to the 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 United States. There have been multiple studies published on the role of IL-6 in DME. In one study published in the peer-reviewed journal Ophthalmology, IL-6 levels in the eye positively correlated with the severity of DME. According to a presentation at the Association for Research in Vision and Ophthalmology at the 2012 annual meeting, IL-6 levels in the eye positively correlated with resistance to anti-VEGF therapies which are among the current standard of care for the treatment of DME.

EBI-031 is an antibody with the potential for a longer half-life compared with approved intravitreal protein therapeutics and illustrates the power of our AMP-Rx platform. Our scientists have critical insights into innovative design concepts that we believe will yield high potency, longer intravitreal residence time, a quicker systemic clearance for EBI-031 and possibly other future antibodies as well.

We have applied for intellectual property in this area and are completing early non-GLP preclinical studies and have started the necessary early clinical manufacturing development to allow us to file an IND by the end of 2015.

During the second quarter of this year, we will be presenting on our programs at both the American Society of Cataract and Refractive Surgery annual symposium and the Association for Research in Vision and Ophthalmology annual meeting.

Along with the addition of Dr. Wendy Dixon, the former Chief Marketing Officer and President of Global Marketing for Bristol-Myers Squibb earlier this year, we have rounded out our Board of Directors with two new members. Dr. Jay Duker is a Professor and Chair of Ophthalmology at Tufts University School of Medicine and a Director of the New England Eye Center. Dr. Barry Gertz is a venture partner at Clarus Ventures, Chief Medical Advisor for Relay Pharmaceuticals, and former Senior Vice President of Global Clinical Development at Merck.

Eleven has been building a Board whose members have complementary expertise to help guide Eleven's success.

I will now turn the call over to Greg Perry to provide a review of the financial results for 2014.

Thanks, Abbie. Earlier this morning we issued a press release detailing our financial results for the fourth quarter and full year of 2014. I will review the financial highlights and speak to our cash position and our financial guidance.

For the fourth quarter of 2014, we recorded a net loss of approximately $8.1 million compared to a net loss of $6.2 million for the same quarter in 2013. Net loss for the full-year 2014 was $34.7 million compared to $21.9 million in 2013.

Total revenue for the fourth quarter of 2014 was approximately $400,000 compared to $500,000 for the same period last year. Revenue was $2.2 million for the 12 months ended December 31, 2014 compared to $1.3 million for the same period in 2013.

Research and development expenses for the fourth quarter of 2014 were $5.3 million compared to $3.2 million for the same period in 2013, an increase primarily driven by EBI-005 related development expenses. Research and development expenses were $26.7 million for the full-year 2014 compared to $13.8 million in 2013.

G&A expenses for the fourth quarter of 2014 were $2.2 million compared to $1.4 million for the same period in 2013 and this increase was driven primarily by higher expenses related to operating as a public company since February of 2014 and increased stock-based compensation expense.

General and administrative expenses were $8.5 million for the 12 months ended December 31, 2014, compared to $4 million for the same period in 2013.

We ended 2014 with $54.1 million in cash and cash equivalents. Based on current operating plans, we believe that we have sufficient cash and cash equivalents to fund our operating expenses, debt service obligations, and capital expenditures into 2016. And as Abbie mentioned, we executed a pipe financing late in the fall which allowed us to provide additional resources for the development of EBI-005 for the treatment of moderate to severe dry eye disease and moderate to severe allergic conjunctivitis. This additional cash also continued to allow us to advance EBI-031 toward the clinic.

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

(Operator Instructions). Jason Gerberry, Leerink Partners.

Good morning. This is Derek on for Jason. I just had a couple of questions. First, can you just give us a sense of what you expect OpEx to look like relative to 2014? And I guess seeming that you are going forward with the AC indication that it might be more back-half weighted to the year?

My second question is as far as the AC indication, can you give us a sense of the size of the trials and the potential cost and are you looking more as like a 3Q start or a 4Q start? Thanks.

Derek, this is Greg. I can start with that and then Abbie and Mike can jump into a little bit about what our thinking is about the trials. I think in terms of operating expense, we are looking at $54 million of cash at the end of 2014 and the guidance for cash getting us into 2016 means basically into that first quarter.

In terms of the profile, I think you would probably see roughly 55% of the expense in the back half of the year versus say 45% in the first half of the year.

Just preliminary thinking, we are not done obviously designing the details of the Phase 3 trial. We are anticipating second half. That is what we are guiding to at this point and in terms of the trial's size, they certainly not as big as dry eye disease trials. They are probably looking at some other folks that are developed in this area. There are fewer than 200 patients and so once we get a little more firm on that design we will have a little more clarity on that. But Abbie? Mike?

So just to confirm what Greg said, we really are targeting the second half of the year. We have been doing a lot of work with our KOLs as advisors as well as with our own team to understand the most efficient and effective trial to move forward. Again, I think as we mentioned, our recent communications with the FDA have given us a lot of direction that we can now implement into our protocol design and our plans and of course we will be continuing to update people as we go.

Great. Then just one follow-up on 031 for DME, do you have a sense of how many patients actually fall into that severe patient population as well as that are resistant to VEGF therapies?

So I don't think that we have really clarified those numbers because the question about who is actually resistant to VEGF therapies right now since it is such a recent approval for the VEGF in DME, that is data that is sort of being generated over time. I don't think that we are exclusively targeting the most severe patients. I think that we are targeting the same patient populations that are being targeted with the anti-VEGFs and we know that it is a fairly significant patient population and we are already seeing a great deal of success in that area for the other VEGFs. Mike, do want to comment?

As Abbie mentioned, it is not only the patients -- we would be looking at (inaudible) patients who are resistant to anti-VEGFs but a big portion of patients have some response to the anti-VEGFs but not a complete response. Those would also be patients that we would be looking at. And there is another opportunity which is decreasing dose frequency.

We know in diabetic retinopathy that patients require far more anti-VEGF injections then they do for other indications. So coming up with a molecule that actually requires lower treatment burden is also an opportunity.

Okay, great. Thanks, guys.

I think that one of these things just as far as the patient numbers, a frame of reference is really that about 10% of diabetics really have diabetic macular edema and as you know, there is an increasing incidence in diabetes these days and so we see this as not only a current unmet need but a growing unmet need.

Thanks, guys.

(Operator Instructions). Liav Abraham, Citi.

Good morning, just following up on the question on EBI-031 for DME, you talked about a longer half-life and less frequent dosing. Is there any additional commentary you can make about the durability of this compound?

Secondly, on the allergic conjunctivitis trials given that these are typically a lot shorter than dry eye trials, any sense on what the earliest could be for a potential filing of this if all goes according to plan? Thank you.

Thank you, Liav. So beading on the DME question first and the longer half-life, what the team has done using the AMP-Rx platform is optimize the structure of the antibody as well as the potency of the antibody that allows for a more durable inhibition of both bound and free forms of IL-6 so comprehensive blockade of all forms of IL-6 for a longer period of time. And while we don't have any data in primates or humans at this point in time, we have seen that in antibodies of these types when we give them intravitreally, there is a fairly predictable scaling that goes between the rodent models to the primate to the human and with that you can sort of predict what the half-life might be as things move.

So right now the half-life of EBI-031 in rodent models and in rabbit models is about 2 times that of the VEGF inhibitors. And so when you combine that with our increased potency, we could actually anticipate possibly getting a durable response for up to three months. So we see that as a significant improvement over the frequency of administration at this particular point in time.

So I hope that that answers the question about the DME longer half-life and durability.

With regard to allergic conjunctivitis, you are absolutely right, these are shorter trials than in dry eye disease and we have the opportunity to leverage a lot of the work that is being done in the dry eye program to support our BLA filing for allergic conjunctivitis as well. So the manufacturing work that is going on for dry eye as well as the longer-term safety exposure that has being done for dry will be supportive of the allergic conjunctivitis filing.

And so with that, we really looked with the two trials and getting everything completed that we could be filing in 2017 for allergic conjunctivitis.

So we are pretty excited about that program and Mike has been working very hard on designs in order to get the best data as quickly as possible and leveraging our understanding of how these trials have been done in the past.

Great. Thank you.

Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect. Everyone have a great day.