CRISPR therapeutics inc, logo 2020

Graphic Source: CRISPR Therapeutics, Inc.

Introduction: What is CRISPR Therapeutics, Inc.?

CRISPR Therapeutics (NASDAQ:CRSP) is a gene-editing company focused on the development and versatile application of CRISPR/Cas9 therapeutics, a special brand of therapeutics used for precision genome editing by applying a viral defense mechanism from bacteria to regulate, disrupt, or correct genes related to key diseases. CRSP is currently targeting disease areas, including hemoglobinopathies, oncology, and regenerative medicines.

Founded in 2013 in Switzerland, CRSP has since grown to over 304 employees producing relatively inconsistent revenues ranging from $3M in 2018 to $290M in 2019 with expectations for 2020 at $6.7M. Their lead candidate is CTX001, an investigational autologous gene-edited hematopoietic stem cell therapy developed in partnership with Vertex Pharmaceuticals (NASDAQ:VRTX) for treating transfusion-dependent beta-thalassemia (“TDT”) and severe sickle cell disease (“SCD”).

Products: CRSP’s pipeline consists of 9 therapeutics: 4 in the clinical phase and 5 in the research phase. Of the 4 clinical phase therapeutics, the first targets TDT and SCD (mentioned above: CTX001), while the 3 others fall into immuno-oncology covering: CD19+ malignancies (Product: CTX110), multiple myeloma (CTX120) and solid tumors and hematologic malignancies (CTX130). All immuno-oncology therapeutics are allogeneic CRISPR/Cas9 gene-edited CAR-T cell therapies wholly owned by CRISPR Therapeutics with data updates typically every 6 months.

Customers/market: For CRSP’s clinical phase pipeline, the total estimated 2022 global market potential is $220B with an average market size for each disease of $36.7B growing at an average 15.2% CAGR (median market: $13.3B | CAGR 10.9%). The largest market is Solid Tumors, at a 2022 estimated size of $145B (8.1% CAGR), and the highest CAGR market CAR T/CD19+ market at a 34.5% CAGR. For CTX001, the lead candidate, the target market can be broken down into the TDT market at very roughly $1.8B with a 10.8% CAGR and the SCD market

Horizon Therapeutics’ (HZNP) competitor Selecta Biosciences (SELB) reported results phase 2 of SEL-212 (pegadricase plus ImmTOR) which failed to beat Krystexxa in refractory gout patients. SEL-212 achieved a numerically better response rate at 3 and 6 months, but the results failed to reach statistical significance. SEL-212 results confirm its prior efficacy profile which is only moderately better than Krystexxa monotherapy and it does not represent an apples-to-apples comparison as SEL-212 has an unfair advantage of the addition of ImmTOR, Selecta’s immunomodulator, to pegadricase, which is the biologic candidate with the same mechanism of action as Krystexxa (pegloticase).

I believe SEL-212’s phase 2 results further solidify Krystexxa’s likely leading position in the refractory gout market given the emerging and very strong combination data of Krystexxa with approved immunomodulators (mainly methotrexate). I expect the combination to achieve much greater efficacy in the ongoing MIRROR study than SEL-212 will in its phase 3 study against placebo.

SEL-212 fails to significantly differentiate on efficacy and completely fails to differentiate on safety

Selecta’s initial pitch to investors on SEL-212 was not only that it should achieve better efficacy than Krystexxa, but that it will also have a better safety profile. In my article on Horizon last year, I noted this trial may not be relevant because of the MIRROR study where Horizon is studying Krystexxa and methotrexate combo. Not only was this trial not relevant, but it was also damaging to Selecta’s valuation given the primary endpoint failure, and it also turned out that there were no differences between SEL-212 and Krystexxa in the phase 2 study in treatment-related side effects, serious side effects, or infusion reactions.

On the efficacy side, Selecta once again resorted to per-protocol (‘PP’) assessments versus intent-to-treat (‘ITT’) assessments, though, granted, it did report ITT data as well. I will only

Dewpoint Therapeutics announced Tuesday that it has raised $77 million in its second round of venture funding, which will help the company continue to target “undruggable” diseases through an emerging field in cell biology.

The Boston-based biotech works on organelles inside cells called biomolecular condensates, which it believes can be harnessed to treat diseases including cancer and rare genetic disorders. Condensates are membrane-less droplets that help cells perform vital functions.

The funding round was led by Chicago-based ARCH Venture Partners, bringing Dewpoint’s total venture financing to $137 million. The deal attracted new investors Maverick Ventures and Bellco Capital, and previous investors Leaps by Bayer, EcoR1 Capital, Polaris Partners, Samsara BioCapital, and Innovation Endeavors also participated in the round.

“Today’s announcement underscores the interest in biomolecular condensates among investors with a track record of backing groundbreaking science,” Amir Nashat, managing partner of Polaris Partners and interim chief executive of Dewpoint, said in a news release.

Since its founding in 2018, Dewpoint has signed deals with two pharmaceutical giants. In July, Dewpoint announced a collaboration with Merck & Co. to work on the treatment of HIV, and in November, Dewpoint announced it would work with German pharmaceutical company Bayer to develop new treatments for cardiovascular and gynecological diseases.

Dewpoint also announced Tuesday that Giuseppe Ciaramella, the president and chief scientific officer of Beam Therapeutics, would join its board of directors. Prior to Beam, Ciaramella worked at Moderna in Cambridge, first as head of immunology and biotherapeutics and then as chief scientific officer of its infectious diseases division.

Anissa Gardizy can be reached at [email protected] Follow her on Twitter @anissagardizy8.

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