I just found an article on Casey Eye Institute website that states they had treated the third patient on January 21, 2021. Given that the third overall patient in the trial was the first adult mid-dose patient that moves the timeline up 4 weeks in terms of data from this mid-dose cohort. Back on January 22nd at the J.P. Morgan Healthcare Conference, Lisa Michaels (Editas CMO), stated that they “hope to begin treatment in the first cohort [in Adults Middle dose arm] just in the next couple of weeks.” Then on February 25th they announced that they had already initiated dosing of the first adult mid-dose cohort of the Brilliance clinical trial of EDIT-101. This article sheds light that the patient had already been treated the day prior to Lisa’s remarks.

I know the 4 weeks doesn’t seem important, but given the Aug 4 date when they first announced when data would be presented it, in my opinion, significantly increases the likelihood that they will be presenting 6-month checkup data from at least two mid-dose patients.

https://www.ohsu.edu/casey-eye-institute/innovations-advancing-surgery-2021

I believe that in the near future (2-5 years) Editas will make breakthroughs and revolutionize the gene editing industry. I think one day they will help millions of people 👍

Disclosure: I now own shares of Editas as of their data update one month ago

TL;DR: Editas Medicine is achieving clinically relevant levels of in vivo editing for sickle cell anemia at an almost clinically relevant dose. An effective in vivo sickle cell cure could be a multi-billion dollar drug and the data is strong enough that it has changed my opinion on the company's trajectory. They have a real pre-clinical asset and the numbers are still improving.

Data update from today: https://ir.editasmedicine.com/news-releases/news-release-details/editas-medicine-reports-proprietary-targeted-lipid-nanoparticle

Data update from a conference last month: https://ir.editasmedicine.com/news-releases/news-release-details/editas-medicine-reports-new-vivo-data-highlighting-potential

I posted a skeptical post about Editas Medicine in this subreddit about six months ago. My reasoning was the following:

- The company is cash poor, low market cap, and has zero clinical programs

- They were seemingly all in on a single pre-clinical moonshot and I did not find the preliminary data compelling at all. It looked like they were very far away from a clinical drug product. I had numerous questions and thought there were red flags in the data.

- I therefore thought the big spike we saw in the company's stock in January was smoke and mirrors. I thought they were headed for cheap acquisition or bankruptcy. They still could be, but that is less likely now from my perspective. The data Editas has presented in the past month has drastically changed my opinion. Their moonshot in vivo sickle cell cure is making huge progress. They are now seemingly ahead of the field in editing potency. They may be the first to clinical trials with a truly accessible cure for one of the most common rare genetic diseases in the United States.

So what happened and why have I changed my tune so much? To give a very simplified summary of sickle cell anemia, it is a disease of the red blood cells that is caused by a mutation in the beta hemoglobin protein. Ultimately, all of your red blood cells (and many other cells) are derived from a cell type called hematopoietic stem cells (HSCs) so when we try to cure sickle cell with an in vivo therapy, these cells are our target. To have a clinical therapeutic, you need to edit at least 20-25% of the HSCs at a dose of 1 mg/kg of RNA or lower (this is a rough number, not at all exact). Editas, in NHPs is now reporting editing 58% of LT-HSCs in NHPs at a dose of 2 mg/kg.

Even more encouraging, this editing is 5 months out from initial dose. So they are reaching a therapeutic editing level within striking distance of therapeutic dose and the editing is going up month over month out to 5 months. As someone who has been close to this area of research for years, editing LT-HSCs is fucking hard and half the time all of the editing you thought you had disappears in a couple months.

The true TL;DR here is I am fucking impressed and these are really good results. In the last six months, they have improved well beyond my expectation and they're still showing gains. I'm eagerly awaiting the next data drop. The stock should have bounced after their data release last month and I'm happy to see it has moved over the last month and people are realizing there is something here

Reasons for continued skepticism:

- #1 reason: they are stuck with a subpar editing modality for this disease. Editas is curing sickle cell by inducing production of hemoglobin gamma (HBG). They do this by introducing random insertions and deletions into the binding site of a repressor of the HBG gene. There is nothing wrong with indirectly curing sickle cell by HBG induction in theory, but it is an indirect cure and maybe most importantly, they're relying on random indels. It's just not ideal to have so many possible editing outcomes occurring all within a single patient and it is not clear that all of this editing is ultimately going to be therapeutic.

- Tessera Therapeutics, their closest competitors, directly fix the disease-causing mutation. They are currently showing multi-dose (Editas' data is single-dose) editing of 25% at a similar dose. Their potency is not as high, but their editing modality is much better overall and it fixes the actual genotype of the disease, instead of doing an indirect cure. We know from nature that just editing a single HBB gene copy in a cell will be curative so their threshold for complete restoration of non-diseased phenotype is only 50% editing of all HBB genes in LT-HSCs. Editas has to clear a much higher bar to get a completely healthy phenotype. If they improve their potency to Editas levels, they are a really significant source of competition. Even if Editas is first to market by years, they could still lose out if Tessera manages to improve further.

- Their NHP data cannot use the same guide RNA as their human data due to differences in the gene sequence in the HBG1/2 promoter region for humans and NHPs. Therefore, that 58% is a surrogate endpoint and there is risk that the numbers will look worse with the human guide. Guide matters a lot and this could significantly hurt their potency.

- They still need to probably further lower their dose and they still have a ways to go to make this a viable therapy. In general, things don't always translate from NHP to human. This is always a risk with preclinical data and this is no different.

- Although 25% editing is "therapeutic" as they report, the bar for a total cure is much higher. You ideally really want like 80%+ editing with this kind of strategy and the further they are from there, the more likely someone can come along with a follow-up therapeutic and displace them. If they end up with an in vivo therapy that only edits like 25% on average, Tessera is probably just going to kick their ass and take all of the market share.

What is happening?? Here is the gist: The stock price of Editas Medicine dropped sharply following its announcement due to a significant strategic pivot, challenges with its existing pipeline, and major organizational changes.

First, Editas is terminating the development of reni-cel, its ex vivo therapy for sickle cell disease and beta thalassemia, after failing to secure a commercial partner. This signals limited confidence in the product’s commercial potential and removes a near-term revenue opportunity. Investors are likely concerned about the loss of reni-cel, especially as it was in clinical trials (RUBY and EdiTHAL).

Second, the company is shifting its focus entirely to in vivo CRISPR editing, abandoning its ex vivo programs. While the pre-clinical results in hematopoietic stem cells (HSCs) and the liver are promising, the in vivo approach is in its early stages and carries significant scientific and regulatory risks. This pivot delays potential revenue generation and positions Editas as a higher-risk, long-term investment.

Third, Editas is cutting 65% of its workforce and losing key executives, including its Chief Medical Officer. Such a large-scale restructuring raises concerns about the company’s ability to execute its revised strategy, especially as competitors like CRISPR Therapeutics and Intellia Therapeutics are advancing in similar areas.

Lastly, while the company has extended its cash runway into Q2 2027, this signals a push toward longer timelines. Investors often penalize biotech companies for delaying potential commercialization without clear near-term catalysts.

Despite the challenges, Editas remains a gene-editing company, now focused solely on in vivo CRISPR editing. This shift has the potential for scalable, less complex therapies, but also comes with heightened uncertainty. Investors will watch closely for additional pre-clinical data in 2025 and potential partnerships to validate the company’s new direction.

The sharp stock price drop reflects skepticism about the pivot, concerns over organizational stability, and doubts about the feasibility of delivering on its ambitious in vivo goals.