Good afternoon, and welcome to Editas Medicine’s Fourth Quarter and Full-Year 2018 Conference Call. All participants are now in listen-only mode. There will be a question-and-answer session at the end of this call. Please be advised that this call is being recorded at the company’s request.

I would now like to turn the call over to Mark Mullikin, Senior Director of Finance and Investor Relations at Editas Medicine.

Sir?.

Thank you, operator. Good afternoon, everyone, and welcome to our fourth quarter and full-year 2018 conference call. Shortly after the market closed, we issued a press release providing our financial results and corporate updates for the fourth quarter and full-year 2018.

A replay of today’s call will be available on the Investors & Media section of our website approximately two hours after its completion. After our prepared remarks, we will open the call for Q&A.

As a reminder, various remarks that we make during this call about the company’s future expectations, plans, and prospects constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995.

Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent quarterly report on Form 10-Q, which is on file with the SEC.

In addition, any forward-looking statements represent our views only as of today, and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements even if our views change.

Now, I will turn the call over to our Chief Executive Officer, Cindy Collins..

Thanks, Mark. Good afternoon, everyone, and thanks for joining us for our corporate update call for the fourth quarter and full-year 2018.

In addition to Mark, I’m joined today by several members of our executive team, including Charlie Albright, our Chief Scientific Officer; Vic Myer, Chief Technology Officer; Andrew Hack, our Chief Financial Officer; and Tim Hunt, our Senior Vice President of Corporate Affairs.

We are at an exciting juncture at Editas Medicine as we enter the clinic with the first in vivo CRISPR medicine to be approved for human testing anywhere in the world.

And we wouldn’t be here today without our dedicated team of editors who are working to translate the promise of CRISPR gene editing into durable medicines that transform patients’ lives. On today’s call, we will review some of what we achieved over the past year and then look ahead to 2019 and beyond.

So, let’s start with just a few of our teams with many accomplishments in 2018. We received permission from the FDA to begin clinical trials with our lead experimental medicine EDIT-101 for LCA10, which we expect to be the first in vivo CRISPR medicine administered to patients in history.

We advanced our potentially best-in-class CRISPR medicine for sickle cell disease and beta-thalassemia, culminating in an oral presentation at the American Society of Hematology in December that was awarded best of ASH by the organizers. We fortified our intellectual property with favorable court rulings and additional patent issuances and filings.

We strengthened the organization with key additions to senior leadership and our board of directors. We expanded and deepened our alliances with Allergan and Celgene, and finally, we maintained our strong capital base providing a robust runway to create transformative medicines for patients and value for shareholders and employees.

These accomplishments give us momentum into 2019 when we plan to initiate patients screening mid-year for the Phase 1, 2 trial of EDIT-101 and to begin dosing patients in the second half in collaboration with our partner Allergan. We expect to begin IND enabling activities for sickle cell disease and Usher syndrome 2A.

We plan to hire outstanding executive leadership to lead our next phase of growth. And lastly, we expect to establish additional strategic alliances to expand and accelerate our development of transformative genomic medicines.

This positions us to achieve our EM22 goals for the year 2022 to have at least three experimental medicines in early stage clinical trials at least two in or ready for late stage clinical trials and all of this built on best-in-class pipeline platform and culture.

Now, let me turn the call over to our Chief Scientific Officer, Charlie Albright to discuss our pipeline progress in more detail.

Thanks Cindy. I’m excited to be with all of you here today to update you on our progress in both our in vivo CRISPR medicines, as well as our engineered cell medicine programs. Starting with the ocular portfolio. We’re developing our lead experimental medicine EDIT-101 for Leber Congenital Amaurosis type 10 in partnership with Allergan.

We’re gratified that the FDA accepted the IND for EDIT-101 upon initial review in November. This is even more notable because as Cindy mentioned, EDIT-101 is poised to be the first in vivo CRISPR medicine administered patients anywhere in the world.

Much of the pre-clinical work for EDIT-101 was summarized in the manuscript that was recently published in nature medicine. The acceptance of the IND and manuscript are tangible examples of the quality of the science we’re doing here at Editas.

We’re planning to start screening patients for the Phase 1, 2 interventional studies in the middle of the year followed by dosing in the second half. We expect to enroll 10 to 20 adult and pediatric patients in this open label dose escalation study to evaluate the safety and efficacy of EDIT-101.

We will test up to three dose levels across five cohorts. We’ll start with a low, but potentially efficacious dose in adults with more severe vision loss. We will then progress to higher doses in adults with a broader range of vision.

Following review of safety data by an independent data monitoring committee, pediatric patients with a range of vision will be included. As we look forward to dosing patients, it’s worth recalling that our preclinical studies in mice and nonhuman primates showed a rapid onset of editing within a few months following dosing.

Productive editing is expected to trigger increase CEP290 protein and thereby growth of the outer segments in the photoreceptors. New outer segments should lead to an ability to sense light and hopefully rescue vision in these patients. As we advance the interventional study for EDIT-101, we’re also conducting a natural history study.

The natural history study can enable the interventional study in several key ways. In particular, the natural history side, let us examine potential end points, identify patients and engage sites. For instance, we have seven sites in this study recruiting across The United States and Europe.

We anticipate that these sites will be part of the Phase 1/2 study and longer-term development of the clinical program. We also expect some demographic and baseline data collected today to be presented at the Retinal Cell and Gene Therapy Innovation Summit in April.

The EDIT-101, the next program addresses another inherited retinal disease called Usher Syndrome type 2A or USH2A. Like LCA10, USH2A affects the photoreceptors.

For these reasons, we can leverage almost the entire product construct from EDIT-101 namely the same AAV vector, the same Staphylococcus aureus Cas9 and the same photoreceptors specific promoter.

We expect that the only difference between EDIT-101 and USH2A therapy will be the guide RNAs and we believe these similarities de-risk and accelerate our development of the experimental medicine for USH2A.

We presented initial data with academic collaborators from Massachusetts Eye and Ear last year and plan to present additional results at the American Society of Gene and Cell therapy in May.

Finally, it’s worth mentioning that our success with Staph aureus Cas9 uniquely positions us to develop gene editing medicines with AAV, because Streptococcus pyogenes Cas9 is too large to enable this single AAV approach we use with EDIT-101.

In addition, with a good progress that we are making in our ocular pipeline to help patients with serious eye diseases, the learnings from our ocular work position us to begin work in other therapeutic areas were in vivo editing could lead to transformational therapies.

Turning next to our programs in engineered cell medicines, the convergence of gene editing in cell medicines is expanding the cause of transformative medicines that are now possible. We are working in a number of different cell types for several serious diseases.

Let’s start with our program to develop a best-in-class engineered cell medicine to treat sickle cell and beta thalassemia. In our approach, we edit sites within the globin locus that increase fetal hemoglobin directly.

At the American Society of Hematology meeting, we showed that cells edit at the globin locus repopulated all lineages of the blood system, including importantly the red blood cell precursors. In contrast, others were editing an enhancer element of the BCL11A gene that indirectly increases fetal hemoglobin.

We found that cells edit at the BCL11A enhancer had reduced levels of red blood cell precursors and lower editing in those precursor cells and survive. If these preclinical results translate to humans, our editing approach for hemoglobinopathy may yield a medicine as both safer and more effective than other gene editing medicines in development.

Our presentation in ASH was selected as one of eleven best of ASH abstracts chosen from a field of over 5,000, again exemplifying the quality of the science at Editas. Later this year, we will present additional data on this exciting program and initiate IND enabling activities.

Switching gears to our work in Oncology, we’re investing significantly to develop engineered cell medicines to treat cancer. We are advancing programs to address liquid and solid tumors using both autologous and allogeneic approaches. We have programs with Celgene on engineered T cells and wholly-owned programs utilizing natural killer cells.

More to come about these programs later in the year. Now, I’ll turn the call over to our Chief Financial Officer, Andrew Hack to discuss how we are building the business and to review our financial results..

Thanks Charlie. It’s my pleasure to update you on key developments in the business and to summarize the financial results we’re reporting today. We made strong progress in building a sustainable and valued business over the past year.

In 2018, as part of our strategic collaboration with Allergan, we and Allergan each exercised our respective options to form a 50-50 co-development and profit-sharing partnership for EDIT-101 in The United States.

As a result of that decision and the subsequent acceptance of our IND for EDIT-101, we received aggregate milestone payments of $40 million from Allergan.

Outside the U.S., Allergan remains responsible for both the development and commercialization of EDIT-101 and we are entitled to milestones and a high single-digit royalty on net product sales in those territories. Allergan continues to be an excellent partner and we look forward to executing our U.S.

development strategy for EDIT-101 with them into years ahead. 2018 was also a year of continued success in expanding and fortifying our robust intellectual property portfolio. We were pleased that the U.S. court of appeals for the federal circuit affirmed the U.S.

pattern and trademark offices’ decision that ended the interference concerning foundational patents exclusively licensed to Editas.

We believe this ruling validates our strategic investment in intellectual property, which includes over 70 issued patents and over 600 pending applications for CRISPR/Cas9 and CRISPR/Cpf1, and continues to expand on a regular basis.

Turning to the numbers, we have summarized our financial results for the fourth quarter and full-year 2018 in the press release that we made available an hour ago and we expect to file our 10-K shortly.

Our cash, cash equivalents and marketable securities increased $40 million in 2018 to $369 million as of December 31, 2018 from $329 million as of December 31, 2017. Our uses of cash totaled $103 million and include cash operating expenses of $98 million and capital expenditures of $5 million.

Key non-cash items recorded in our income statement include $27 million of stock-based compensation, $14 million of non-cash R&D charges associated with payments to our license and the acquisition of assets from I2 Pharmaceuticals; $3 million of depreciation and a $3 million increase in working capital.

Over the course of year, we grew the size of our organization by approximately 20% increasing to 132 full-time employees from 112 at the end of 2017.

The primary drivers of growth in our spending in 2018 were our expanding and maturing pipeline and advances in our platform, and we expect these to continue to be the primary drivers of spending growth in 2019.

Our sources of cash in 2018 totaled $143 million and consisted of $77 million of equity capital raise, $50 million of milestone payments from our business development partners, $11 million of stock purchase by our employees through stock option exercises, and our employee stock purchase plan, and $5 million from various other sources.

We believe our year-end cash position of $369 million provides at least 24 months of capital to fund the advancement of multiple transformative experimental medicines. And with that, I hand it back to Cindy..

Thanks, Andrew. Before we wrap up our prepared comments, let me briefly remark on our organizations transition to the next phase of growth. We have continued to strengthen the board of directors with my recent appointment and the addition of Dr. David Scadden announced just weeks ago.

And as you know, we are also in the midst of changes to our executive team. I would like to thank our departing CEO, Katrine Bosley; and CFO, Andrew Hack for their leadership in building Editas and advancing us toward the clinic with our first experimental medicine.

We have active searches for both positions underway with the assistance of leading executive search firms and look forward to appointing outstanding new leaders as we become a clinical stage company.

We have an exciting year ahead of us as we enter the clinic with our first experimental medicine that we expect to demonstrate the promise and potential of CRISPR technology to transform patients’ lives. We expect this to be the first of many as we advance our pipeline in 2019 and beyond. We thank all of you for your interest and support.

With that, we will open up the call for Q&A..

Thank you. [Operator Instructions] Our first question comes from Matthew Harrison with Morgan Stanley. Your line is open..

Hi, this is Hana on for Matthew. I was just wondering at what stage are your allogeneic programs at and what are some key differentiating features in your approach versus other CRISPR companies? Thanks..

So, this is Vic Myer, Chief Technology Officer. We did recently disclose high efficiency multi-gene editing and some strategies to ameliorate translocations at the recent Keystone Genome engineering meeting. We haven't disclosed the specific nature of the programs or indications that we're going after at this point..

Okay. Thank you..

Our next question comes from Cory Kasimov with J.P. Morgan. Your line is open..

Hi, guys. Thanks for taking my question. This is Matthew on for Cory.

Just curious on the health of your [indiscernible] collab and interest in natural killer cells, curious to figure your high-level thoughts and how you see autologous CAR T approach is fitting into your role strategy on oncology going forward?.

We really can’t comment too much on the autologous question. That’s really a part of our collaboration as you appreciate with Celgene, and we’re excited about the tremendous progress we’ve made there. We achieved four technical milestones there. What I can say, we are excited about natural killer cells.

We think they are a different kind of cell that has tremendous potential to be effective in our oncology and you will hear much more about our efforts in that area as the year goes on..

Okay, great.

And then on your beta-globin program, what are your thoughts on potential differentiators when compared to gene therapy in both beta-thal and sickle cell disease?.

Obviously, they are different approaches. And there really isn’t a head-to-head comparison that approaches at this point. I think that CRISPR has – gene editing has some significant advantages and that we’re recreating what human genetics have led us to, which is to make mutations in the beta-globin locus that increase fetal hemoglobin.

And so, in that sense I think we’re trying to recapitulate where human genetics has led. I think that’s an interesting way to go..

Great. Thanks for taking my questions..

The next question comes from Whitney Ijem with Guggenheim. Your line is open..

Hi, guys. Thanks for taking the question. Sorry if I missed this.

But just wanted to circle back to USH2A, can you talk about the synergies there between the programs, between that and LCA10 and just wondering if there is ability to leverage some of the pre-clinical package to advance into the clinic more rapidly?.

There are tremendous synergies, this is Charlie. There is tremendous synergies between those two programs and so the therapeutic approach is quite similar that we are going to deliver the gene editing machinery within a single adeno-associated virus.

And because we’re delivering to further receptors in both programs, we'll be able to use the same promoter, the same AAV5 serotype and the same – everything will be the same except for the guide RNAs.

And so, the basis we’ve constructed in the pharmacology models and how we constructed safety package in our experience with the FDA, we all expect to be leverageable in USH2A program, exactly how that plays out in the details of the timeline we don’t really know, but we clearly have done the USH2A program much more rapidly in the discovery phase with or without the LCA10 program..

Great. Thanks..

Our next question comes from Phil Nadeau with Cowen & Company. Your line is open..

Good afternoon. Thanks for taking my questions. First on the initiation of the clinical trial.

Can you talk in a little bit more detail about what has to happen between now and when the first patients are screened, is the bottlenecks manufacturing, is there opening the clinical trial sides, and what are the workstreams that will take several months?.

We’re doing all the things you just mentioned and more. So, we have got the IND approved. We need to get IRB approval and Institutional Biosafety Board approval. We have to get the patients screened and we then eventually have to get them scheduled for what’s a surgical procedure on top of delivering the drug obviously to the site.

So, I think you can appreciate in these rare diseases that you just can’t turn on the stick in the same way you would in a more common disease or in a trial where you're enrolling healthy volunteers. So, it’s really all the things that go up to the ability to actually dose a patient..

And do you have the drug manufactured or the therapy manufactured for – in order to dose the full trial or is there still a manufacturing run that must happen?.

So, as – I’m sure you’re aware, in order to get the IND approved we’ve had to have several development runs, as well as GMP compatible runs. So, we're comfortable with our process and we’re comfortable with our network..

Got it. Okay.

Second, on the Celgene collaboration, obviously you may or may not be subject to take out, is there any change of control provision in that collaboration or does your collaboration go unmodified even if Celgene is part of a bigger organization?.

Hi, Phil, it’s Andrew. No. There’s no change of control that changes the nature of the agreement. So, Celgene has acquired or Celgene is not acquired the collaboration will continue as planned..

Got it. Andrew congrats on your tenure at Editas. One other financial question for you.

On the milestones in Allergan transaction, can you remind us how they are booked, are they amortized over the life of the agreement?.

Yes. The $25 million IND acceptance milestone is treated differently than the $15 million milestone associated with the opt in. And so, we didn’t take it through the accounting in some more detail, but the 25 actually gets treated as contingent consideration and is added to the pool of deferred revenue that gets brought in over time..

Got it. Okay. And then one last question from me that’s on the patent landscape.

First is on the University of California patent that was just issued, what are your perspectives on that patent and second are there any patent developments that we should look forward to over the next couple of months or quarters?.

I’ll take that one as well Phil, thanks, and thanks for the congratulations. The patent that was recently allowed is one of the patents that was involved in the interference. We expect it to be allowed with the interference having cleared. I think this is obviously a top of the horizon much more detailed discussion, but feel really good about our IP.

This issuance doesn't affect any of our IP, which we think covers all medicines using CRISPR technology.

And I think it's also worth just noting that the way this patent is issuing and some others from UC, are structured, they have key constraints on the guide RNA structure that’s covered under that patent, and I think it’s worth just reading those clients in some details to understand those constraints better..

Got it. That's very helpful. Thanks again for taking my questions and congrats on your transition..

Thanks, Phil..

Our next question comes from Amanda Murphy with BTIG. Your line is open..

Hi. Thanks for taking the questions. Good afternoon. Just actually had a follow-up on Celgene, I think you’ve presented some data in the past around T cell editing using Cpf1.

So, is that part of the Celgene agreement correct? And then also just curious, I know you probably have a lot going on, but have you had any discussions at this point about kind of extending the agreement beyond 2020 rates or anything in terms of extending beyond that and have you had those discussions yet?.

So, this is Vic. I’ll take that question. Yes. We’ve shown highly efficient editing in T-cells with Cpf1 multiple genes and in fact for all the sort of most likely genes for an allogeneic package.

We’ve shown multiplexing of Cpf1 in primary cells as well and we’ve shown that combining Cas9 and Cpf1 actually reduces the frequency of observed translocations. I can't comment on the nature of the discussions around prolonging the relationship with Celgene..

Okay got it.

And then just on Cpf1 it seems like there is patents being issued every day on in new enzymes, new CRISPR enzymes, just curious if you are seeing anything else that’s out there that’s interesting that has as clinical advantages that you might want to bring in-house whether it be smaller enzymes or ease your delivery – or packaging into delivery system?.

Yes. So, we of course keep an eye on the literature and there’s a lot people are working on creating or discovering new molecules. We’re really happy with both Cpf1 and Cas9. All the versions of Cas9 that we use. They’re complementary in many ways. We can package them up in an AAV and so we feel really good about those.

I think the bar for new enzyme would have to be very high. We’re at 95% or better editing with our two different platforms..

Okay. This is my last question. Kind of continuing that theme. So, given you have Cpf1, I mean obviously you are maybe one of the only CRISPR companies to be able to use a single AAV in terms of delivery.

And then obviously, you put a lot of work into your guide RNA structure and you might have a little bit of a unique technique or strategy there as well.

So, just curious if you are seeing interest from pharma partners in terms of maybe moving into other indications based on those two factors I mentioned?.

Yes. So, this is Vic again.

I mean, we spend a lot of time talking to a lot of people and there’s a lot of focus on the field, it is probably inappropriate for me to do disclose who we’re speaking with, but I think one of the things that we have shown will continue to show is some of the great advantages that Cpf1 has and how it differentiates itself from Cas9 and there are certainly folks interested in those molecules..

Got it. Thanks very much..

Our next question comes from Gena Wang with Barclays. Your line is open..

Hi, this is Peter for Gena. Thanks for taking the questions. In terms of EDIT-101, could you give us some color in terms of what happens after dosing, in terms of time line? How long is a waiting period between patients within a cohort and between the courts if any.

And will there be DSMD reviews between cohorts and or between patients? And I have a follow-up..

Multiple questions is better. Most of which we haven’t disclosed. Suffice it to say that the Phase 1/2 trial will be very similar to other gene therapy trials and there will be a delay between patients and small delay between cohorts.

At times there will be an independent safety data monitoring review, but that will not happen between every cohort and will primarily happen to head into pediatric patients. And so – but the rest of the timing you would not be surprised by from what’s happened in gene therapy trials..

Got it. That’s helpful. Just in terms of just management organizational changes, would you be able to give us any color on what type of changes to just your strategic decisions that we could expect any discussions that or any visibility into when new leaderships might be in place? Thank you..

Sure. This is Cindy. And we have no change in our strategic direction at all. We are focused on EM22 as I stated in my earlier comments and continue to focus on that as our overall guiding strategy for the company. In terms of recruitment of other C-level positions such as CEO, CFO, again as I mentioned, we have searches underway.

I’m not going to comment on timing because it’s just too uncertain, but we feel very good about the searches the company is in, and incredibly strong position. We have outstanding science and a leadership team and getting ready to go into the first clinic, lots of cash in the bank. So, all really strong.

Things that candidates would be considering as they think about joining Editas..

Great, thank you very much..

Thank you. [Operator Instructions] The next question comes from Peter Lawson with SunTrust Robinson. Your line is open..

Thanks for taking my questions.

Just – I guess as we think about the natural history Charlie, is that still a first half event?.

We will be presenting baseline data in the early part of this year, hopefully, at the retinal meeting that we discussed in the prepared remarks. It’s important also to realize that the natural history study is not gating in any way for the interventional study.

And we have a good idea of how get that going into the natural history study does other things for us other than start the interventional study..

Got you.

And then what can be seen that study? And how will the data be presented?.

We’re looking at the state of a couple of things. Whether the potential end points that we might use in the interventional study, but it does several other things for us.

It gets the sites up and going, which should dramatically improve this feat of the interventional study and it also begins to identify potential patients for the interventional study. And those are both really important events as you can appreciate recruiting in these rare diseases is one of the challenges in making them grow as quickly as possible..

And then data for the 101, could that be a 2019 event or how should we think about when we could see that data and what kind of readouts we should have and the timing around that?.

We haven’t disclosed that. As you can imagine we are going to be monitoring the day in real-time. We are going to be working with our partner Allergan to decide on the right way to disseminate that data.

As you can appreciate there is always the trade-off between wanting to release every piece of data in real time in the notion of being cautious about how we release the data. So, we’re confident when we see the interpretation and so we will be balancing those competing interest as we think about how to release the data..

And then just finally on the cancer program, could you remind us how long is left on the Juno relationship? And any timing you know around IND studies coming out of that program?.

Yes. The Juno, now Celgene relationship goes till May 2020 as disclosed in our documents and as the program is transitioned to Celgene, our ability to disclose details of the timing of the programs has changed pretty dramatically as you can appreciate with a large pharma partner now, and so unfortunately, we can’t say too much about that..

Okay. Thank you so much for taking the questions..

Thank you..

Our next question comes from Steve Seedhouse with Raymond James. Your line is open..

Hi, good afternoon. Andrew, best of luck in your new endeavor. Just had a question about the LCA10 preclinical data publication from last month. The highest dose of EDIT-101 in mice in that study does not actually read to the highest editing rate, so pretty interesting result, it dips below the editing rate of a lower dose.

The explanation in that paper was for reasons that are unclear at this time.

Obviously, we are not under peer review on this call, so, I’m just curious are there any reasons that you can point to that might be leading to that result?.

No, we don’t actually understand the reason for that result and it could be for all kinds of different reasons, which is why we didn’t speculate in the paper and it is important to realize if that dose is well beyond the dose we anticipate using in humans..

Okay.

The ratio or proportion of productive edits versus non-productive change depending on the concentration of Cas9 local to the DNA?.

No, it does not. But I think entire editing profile is dose independent..

Okay.

And do you know if the AAV5 capsids in the eye can aggregate?.

No, we don’t know the answer to that. What we know is that very similar to other AV programs you do, you do generate an immunogenic response to the capsid and the capsids are transient because there's no way to re-express them once the virus is unloaded if you will..

Alright. Thank you..

Thank you. And I’m not showing any further questions at this time. I’d now like to turn the call back over to Ms. Cindy Collins, CEO for any closing remarks..

Great. So, with that, we thank you all for participating in today’s call and for your support as we work to bring transformative new medicines to patients. Have a great evening..

Ladies and gentlemen, thank you for participating in today’s conference. This does conclude today’s program and you may all disconnect. Everyone, have a wonderful day..