10 Rare Diseases Specialist Stocks

Rare Diseases – Curing The Incurable

While not entirely solved, a lot of major deadly illnesses that have plagued humanity have become more manageable over the last century, from bacterial (antibiotics) and viral (vaccines) infections to diabetes (insulin).

There is, however, a wide array of rare diseases which are still mostly incurable. Most of the time, this is because these diseases are not caused by an external threat, but by a biological dysfunction inside the very cells of the patient. This is quickly changing, thanks to progress in biosciences.

On one hand, with the human genome sequenced and much more advanced analytical methods, scientists can finally understand what are the root causes of rare diseases. Even AI is now helping interpret the data and provide new insights.

On the other hand, new technologies like gene editing open the possibility of fixing deficient cells or organs, restoring normal function.

Rare diseases each affect less than 1 in 2,000 people, with more than 6000 different rare diseases. Despite their individual rarity, together, they affect around 4% of the population, with as many as 30 million people in just Europe.

3/4 of rare diseases affect children, 72% are genetic in origin, and it takes on average 5 years for rare disease patients to get a diagnosis.

1. CRISPR Therapeutics

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a recently discovered tool for genetic editing. It allows for very precise and directed gene editing, and its discoverers have won the 2020 Nobel Prize.

Source: Lab Associates

What sets CRISPR Therapeutics apart is the all-star team of founders, including Dr. Emmanuelle Charpentier, one of the co-discoverers of CRISPR-Cas9 technology.

CRISPR Therapeutics is developing an efficient and versatile CRISPR/Cas9 gene-editing platform for therapies to treat hemoglobinopathies, cancer, diabetes, and other diseases.

The first therapy that they were advancing was targeting the blood diseases β-thalassemia and sickle cell disease.

They have now been approved under the commercial name of Casgevy for both applications, making it the first -ever approved CRISPR gene therapy. Sickle cell and beta-thalassemia are major rare diseases, and the treatment comes with a $2.2M per therapy price tag.

In the long run, they are working on making this gene therapy doable in-vivo (instead of the current ex-vivo approach, requiring expensive and complex extraction of the patient marrow cells first).

The company is working on several other rare diseases, notably:

• Duchene’s Muscular Dystrophy (DMD): IND-enabling stage (Investigational New Drug)
• Acute hepatic porphyria: IND-enabling stage.
• Myotonic Dystrophy Type-1 (DM1): preclinical
• Cystic Fibrosis: Pre-clinical
• 2 other undisclosed rare disease programs.

The company’s first allogeneic CAR-T program targeting B-cell malignancies (cancer) is also in clinical trials.

Another major potential for CRISPR Therapeutics, although not about rare diseases, is in curing type-1 diabetes. This was previously done in collaboration with Vertex but this link was severed in January 2024.

You can also read more about CRISPR Therapeutic in our article “Gene Editing: CRISPR Therapeutics vs. Beam Therapeutics.”

2. Bluebird Bio

Together with CRISPR Therapeutics, Bluebird was the other company granted approval in December 2023 for a gene therapy on sickle cell disease, under the commercial name Lyfgenia. The same therapy is also approved for beta-thalassemia, under the commercial name Zynteglo.

Lyfgenia didn’t make use of CRISPR. Instead, it went the “traditional” route of gene therapy treatment by utilizing a lentiviral vector (LVV), a family of viruses, to modify genes.

Here, the blood stem cells of SDC patients are genetically modified to produce a special hemoglobin HbAT87Q, which functions much like any normal adult hemoglobin but is gene-therapy derived and delivered to the patient.

The company’s success in approval of Lyfgenia has not really translated into success for its stock price. However, the success of the company in getting a total of 3 approved gene therapies using LVV is an indication of its expertise in using viruses for gene therapy.

The commercial success of Lygenia/Zyntelo will be crucial to the future of the company, as its pipeline seems to not contain many other products.

3. Editas Medicine, Inc.

Editas was founded by CRISPR-Cas9 discoverer Jennifer Doudna. Editas started working with Cas9 but is now focused on a proprietary version of Cas12 that they engineered: AsCas12a.

You can read more about Cas12a’s unique properties in our dedicated article “What Is CRISPR-Cas12a2? & Why Does It Matter?”.

To resume it shortly, Cas12as is unique because:

• Hard-to-solve problems with Cas9 could be workable with Cas12a
• It results in higher chances of gene editing happening than with Cas9.
• More than one gene can be modified at once with CAs12a.

Source: Editas

You can also read an overview of all of Jennifer Doudna’s companies in the corresponding article “Top Jennifer Doudna Companies to Watch.”

Editas is most advanced in Sickle Cell Disease (SCD), with 40 patients in a clinical trial at phase 1/2. The first results are expected by the end of 2023 but are still not announced as of May 2024. Overall Editas is behind its competitors in gene therapy for SCD.

Source: Editas

As this therapy and innovative treatments for this disease are seemingly becoming a little crowded, investors will want to look in-depth at the clinical trial results and assess if AsCas12a is producing superior results to “classic” CRISPR Therapeutics Cas9 technology, which is already approved.

However, Editas seems ahead in another rare disease, Leber Congenital Amaurosis (LCA). After a break in 2022, Editas Medicine announced in May 2024 that the clinical trial for EDIT-101 has seen 79% of the 14 clinical trial participants experience measurable improvement after receiving the experimental gene therapy. We discussed these results and the overall news about CRISPR-based gene editing in our article “From Blindness to Meat Substitutes: CRISPR Gene-Editing Continues to Produce Promising Results”.

4. Beam Therapeutics

The company was founded in 2017, focusing on developing the technology of “base editing.” This promises more precise gene editing than traditional CRISPR-Cas9 technology. It could also edit multiple spots in a gene or multiple genes at once.

“Many existing gene editing approaches are like ‘scissors’ that cut the genome. Base editors are like ‘pencils’ that enable erasing and rewriting one letter of the genome at a time.” – Giuseppe Ciaramelle, President & CSO at Beam Therapeutics

Beam Therapeutics is at an earlier stage than other CRISPR companies, with its manufacturing facilities expected to start only in late 2023. Most of its pipeline is still at the research stage of entering phase 1 of 2 of clinical trials.