Crispr Therapeutics AG (CRSP)

[janetcanada]

CRSP - Interesting Video from Dylan Jovine

DYLAN JOVINE CLAIMS THE NEXT BIG BIOTECH TAKEOVER IN 2020 WILL BE A” CUT AND PASTE” COMPANY

"This report tells you everything you need to know about this incredible company --- and why the world’s leading scientist believe its CRISPR technology is the best, giving you the chance to for a 46,751% return"


<< It could help you achieve the kind of carefree retirement most people only dream of. But what if this turns out to be your biggest opportunity? How long will you stay in the dark>>? Continue reading...

[jondoeuk]

Based on the data for CTX110 (a first-gen CD19-targeted CAR-T), and discussions with regulatory agencies, the company initiated a PhII single-arm potentially registrational trial, which incorporates consolidation dosing.

Also, could have feedback from regulatory agencies for CTX130 (another first-gen CAR-T, but CD70-targeted) mid-year. I know they are hoping to move it into another registrational trial in certain R/R T-cell lymphomas.

[NY1972]

Another bio with endless research in crowded field, can't beat AUTO, can't salvage AUTO relapsed. Just lots of hype from crispr to keep printing shares.

[jondoeuk]

Slide deck http://ir.crisprtx.com/static-files/ce2efeb9-3319-4504-8430-13058b305455

[jondoeuk]

The therapies for SCD could be cost effective even with a $2M price tag, the ICER says in a draft report analysing two https://endpts.com/at-2m-per-shot-icer-says-two-new-sickle-cell-gene-therapies-could-be-cost-effective/

[Windbag1014]

Investment analysts at Cantor Fitzgerald started coverage on shares of CRISPR Therapeutics (NASDAQ:CRSP - Get Rating) in a research note issued to investors on Thursday, The Fly reports. The brokerage set an "overweight" rating and a $72.00 price target on the stock. Cantor Fitzgerald's price target suggests a potential upside of 65.63% from the company's current price.

https://www.marketbeat.com/instant-alerts/nasdaq-crsp-a-buy-or-sell-right-now-2023-04-13/

[jondoeuk]

Both are now recruiting. For the CTX131 trial (n=250) unlike CTX130, which was tested in just patients with R/R ccRCC, 131 is open to patients with cervical, esophageal, pancreatic, or malignant pleural mesothelioma.

[jondoeuk]

An historical milestone https://finance.yahoo.com/news/vertex-crispr-therapeutics-complete-submission-120000960.html

The companies are requesting Priority Review.

[jondoeuk]

VRTX has signed a licensing deal to accelerate development of its hypoimmune cell therapies for the treatment of T1D https://www.fiercebiotech.com/biotech/vertex-goes-back-crispr-well-paying-100m-upfront-exa-cel-partner-help-diabetes-work

[janetcanada]

CRSP - From: Simply Wall St™

***Revenue is forecast to grow 49.88% per year

*Pass
Are revenue and earnings forecast to grow?

Earnings are forecast to grow by an average of 52.4% per year for the next 3 years
Section 2.1

*Pass
Are they in a good financial position?

They have sufficient cash for at least 1 year of operations
Section 4.4

Pass
Is their dividend sustainable?

They do not pay a dividend
Section 5.0

*Pass
Is their share price liquid and stable?

Share price has been stable over the past 3 months

Pass
Do they have sufficient financial data available?

They have sufficient analyst coverage
Section 2.0

Pass
Are there any concerning recent events?

No concerning events detected

Pass
Do they have a meaningful market capitalization?

Market cap is meaningful ($4B)
Section 8.0

*Pass
Do they have negative shareholders equity?

CRSP does not have negative shareholders

***CRISPR Therapeutics NasdaqGM:CRSP Stock Report

***Simply Wall St
https://simplywall.st › ... › Pharmaceuticals & Biotech
====================================================

***Founded Employees CEO Website
2013 458 Sam Kulkarni https://www.crisprtx.com
CRISPR Therapeutics AG, a gene editing company, focuses on developing gene-based medicines for serious diseases using its Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) platform. Its CRISPR/Cas9 is a gene editing technology that allows for precise directed changes to genomic DNA. The company has a portfolio of therapeutic programs across a range of disease areas, including hemoglobinopathies, oncology, regenerative medicine, and rare diseases.

The company’s lead product candidate is CTX001, an ex vivo CRISPR gene-edited therapy for treating patients suffering from transfusion-dependent beta-thalassemia or severe sickle cell disease in which a patient’s hematopoietic stem cells are engineered to produce high levels of fetal hemoglobin in red blood cells. It also develops CTX110, a donor-derived gene-edited allogeneic CAR-T investigational therapy targeting cluster of differentiation 19; CTX120, a donor-derived gene-edited allogeneic CAR-T investigational therapy targeting B-cell maturation antigen for the treatment of relapsed or refractory multiple myeloma; and CTX130, a donor-derived gene-edited allogeneic CAR-T investigational therapy targeting Cluster of Differentiation 70 to treat various solid tumors and hematologic malignancies. In addition, the company develops VCTX210, a gene-edited immune-evasive stem cell-derived product candidate for the treatment of treatment of type 1 diabetes; and VCTX211, an investigational, allogeneic, gene-edited, stem cell-derived product candidate for the treatment of T1D. It has strategic partnerships with Bayer Healthcare LLC, Vertex Pharmaceuticals Incorporated, ViaCyte, Inc., Nkarta, Inc., and Capsida Biotherapeutics.

CRISPR Therapeutics AG was incorporated in 2013 and is headquartered in Zug, Switzerland.

[jondoeuk]

This will be an oral presentation (of preclinical data) at AACR next month.

Using AI and machine learning, they did a very simple set of experiments in a robust fashion, which is to take thousands of different edits without any bias and to do them pairwise to see what was going to increase the potency of the CAR-T cells. One of those edits is TGFBRII knockout and the other one is a Regnase-1 knockout. Not only did the latter come out of a large empirical screen in one of the partnerships the company had, but other groups have shown each can improve antitumour activity https://insight.jci.org/articles/view/133977 https://www.nature.com/articles/s41586-019-1821-z

So that combination of edits in preclinical testing, is at least tenfold better, if not more. Also, in their manufacturing process, the expansion of these cells is a lot greater, and the CEO has said they have seen a greater proportion of the central memory genotype phenotype https://ashpublications.org/blood/article/127/24/2980/35453/Phase-1-studies-of-central-memory-derived-CD19-CAR

When they start dosing patients, will know quickly what the PK/PD profile looks like for CTX112 and CTX131. If the expansion at DL1, let's say, is tenfold higher for these CAR-T's, the therapy should be more potent and work better.

Using CTX131 in R/R ccRCC, the first thing will be those expansion kinetics and the second will be responses. Assuming those responses are at low doses than with CTX130 it would inform them as to how they will think about investments, because if they start seeing those signs, will be going to go pedal to the metal on other CAR constructs and targets, with the off-the-shelf platform, especially now they have their own manufacturing.

[janetcanada]

CRISPR Therapeutics to Present at the American Association for Cancer Research 2023 Annual Meeting
March 14 2023 - 06:02PM
GlobeNewswire Inc.
Alert
Print
Share On Facebook

CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, today announced an oral presentation of preclinical data at the American Association for Cancer Research (AACR) 2023 Annual Meeting, taking place April 14 – 19, 2023, in Orlando, FL.
Title: CTX112 and CTX131: Next-generation CRISPR/Cas9-engineered allogeneic (allo) CAR T cells incorporating novel edits that increase potency and efficacy in the treatment of lymphoid and solid tumors
Session Type: Drug Development Special Track Session
Session Title: New Drugs on the Horizon: Part 1
Location: Tangerine Ballroom 2, Convention Center
Date and Time: April 16, 2023, 1:25 – 1:40 p.m. ET

The data are embargoed until the beginning of the Drug Development Special Track Session: New Drugs on the Horizon: Part 1 at 1:00 p.m. ET on April 16, 2023. A copy of the presentation will be available at www.crisprtx.com once the presentation concludes.

About CRISPR Therapeutics
CRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic partnerships with leading companies including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Boston, Massachusetts and San Francisco, California, and business offices in London, United Kingdom. For more information, please visit www.crisprtx.com.

Investor Contact:
Susan Kim
[phone]
[e-mail]

Media Contact:
Rachel Eides
[phone]
[e-mail]

[jondoeuk]

CTX112 and CTX131: Next-generation CRISPR/Cas9-engineered allogeneic (allo) CAR T cells incorporating novel edits that increase potency and efficacy in the treatment of lymphoid and solid tumors https://www.abstractsonline.com/pp8/#!/10828/presentation/2975

[OldAIMGuy]

CRSP current short interest is approx 15%. With upward stock price movement since the start of the New Year, short sellers may re-think their positions.



Accumulation is improving.

Best wishes,
OAG

[jondoeuk]

They are also working on iPSC-derived CAR-NK cells as well. Still early, but more advanced (at least reading some of the patents) than CAR-T.

[jondoeuk]

From this: ''Ultimately, Kulkarni says, CRISPR Therapeutics aims to move to iPSC-derived CAR-T cells as well, but its effort in this area is still early.'' https://www.nature.com/articles/d41587-021-00027-1

[hunterj20]

Scalped an easy 15% here in no time.

[hunterj20]

YES! In my 401k now at $41

[SpaceTimeRift777]

Good Entry for Long

[OldAIMGuy]

I have patience and don't mind the gyrations in price in the mean time. After Tax Selling Season we'll see if the price/share stabilizes and starts to recover.

Best wishes,
OAG Tom

[Hawkins_F33]

I think that people are not truly seeing the value in some of these biotech companies right now. Yes they may be down and yes there is competition but in 10-15 years the investors who got in early will benefit greatly.

[OldAIMGuy]

Motley Fool article brings gene editing into focus:
https://www.fool.com/investing/2022/12/27/could-crispr-therapeutics-help-you-become-a-millio/?source=eptyholnk0000202&utm_source=yahoo-host&utm_medium=feed&utm_campaign=article

Best wishes,
OAG

[OldAIMGuy]

CRSP sports a 16+% short interest position right now. I think that's the highest I've noticed it recently. There's certainly been a down draft in the share price since July so maybe that's part of the reason. I added 12% more shares to inventory this AM.

Best wishes,
OAG

[jondoeuk]

Neogene plans to do the same https://www.fiercebiotech.com/biotech/astrazeneca-forges-deeper-cell-therapies-200m-takeover-solid-tumor-tcr-biotech

[jondoeuk]

PRs https://finance.yahoo.com/news/vertex-crispr-therapeutics-present-american-130000205.html https://finance.yahoo.com/news/crispr-therapeutics-provides-ongoing-phase-150000313.html

Exa-cel http://ir.crisprtx.com/static-files/7e00a1b8-667f-4254-8e45-4057c9a67493

CARBON http://ir.crisprtx.com/static-files/c1419057-b161-4335-a003-41ff46a44bdb

[north40000]

https://www.nature.com/articles/d41586-022-03676-7

[jondoeuk]

ASH abstracts

4629 CTX110 Allogeneic CRISPR-Cas9–Engineered CAR T Cells in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Results from the Phase 1 Dose Escalation Carbon Study https://ash.confex.com/ash/2022/webprogram/Paper166432.html

2137 Efficacy and Safety of a Single Dose of Exagamglogene Autotemcel for Transfusion-Dependent ß-Thalassemia https://ash.confex.com/ash/2022/webprogram/Paper166881.html

12 Efficacy and Safety of a Single Dose of Exagamglogene Autotemcel for Severe Sickle Cell Disease https://ash.confex.com/ash/2022/webprogram/Paper162353.html

[jondoeuk]

SITC titles

CTX130 allogeneic CRISPR-Cas9–engineered chimeric antigen receptor (CAR) T cells in patients with advanced clear cell renal cell carcinoma: Results from the Phase 1 COBALT-RCC study

CRISPR/Cas9 gene-edited, allogeneic anti-CD83 CAR-T cells demonstrate potent activity in GvHD and AML tumor models

[jondoeuk]

CRSP continues to expect to move multiple programs utilising in vivo approaches into the clinic in the next 12 to 18 months, including programs in cardiovascular disease. The company’s lead program, CTX310, targeting angiopoietin-related protein 3 (ANGPTL3) is currently in IND-enabling studies. Also, CTX320 (LP(a)) and CTX330 (PCSK9) are at the research stage, but they could combine all three. In addition, they have established CRISPR-X, a dedicated group within that focuses on emerging technologies, including those to allow HDR-independent and/or AAV-free whole gene correction and insertion.

[north40000]

https://www.the-scientist.com/news-opinion/first-person-dosed-in-novel-gene-editing-clinical-trial-70223

[jondoeuk]

Slides http://ir.crisprtx.com/static-files/5c256eb5-4982-4e47-b463-79eff954e622

[jondoeuk]

Link to webcast https://media.rampard.com/WebcastingAppv5/Events/Registration/registration.jsp?Y2lk=MTkwMw==&Y2lk=MTkwMw%3D%3D

[NY1972]

Too bad GNCA NPT with CAR knock in + PD1 will never be tested. ACT with CART targeting multiple neoantigens will be as potent and more durable.

[jondoeuk]

They start with healthy donor fibroblasts, reprogram to create an iPSC pool and engineer using CRISPR (anti-MICA/B CAR, CD38 KO, IL-15RF and hnCD16 KI). After, comes single-cell sorting and screening of individual clones. The latter for extensive characterisation prior to master cell selection.

For that they look at clones with copy number and locus-target verification, maintain pluripotency, free of reprogramming vectors, demonstrate genomic stability, without off-target edits, ideal propensity to become NKs, as well as desired functional activity and specificity.

[NY1972]

500 clones from different editing sequences? What gets knock in/out first? Are these trade secrets?

[jondoeuk]

Either they make all the edits at the iPSC stage or make a few foundational edits. If it's the latter there would be at least a second round of engineering, going through the sub-clones and then banking.

As for any DNA mutations/translocation they are detectable in the clonal population and can be screened out. I know FATE had to screen over 500 clones to find just a single one to create FT536.

[NY1972]

That is a lot of man made mutations. Hard to believe there is no risk or downside when the T cell genome is cut and paste at will. How do they determine the sequence of the edits?

[jondoeuk]

They haven't publicly disclosed anything (yet), but the route for iPSC-derived NKs could be knockout of the B2M gene and a knock-in encoding SERPINB9, IL-15 fusion, and/or HLA-E. Also, knockout of the CIITA gene and a knock-in encoding the CAR construct. In addition, knockout of ADAM17, FAS, CISH, and/or REGNASE-1.

[NY1972]

How many gene edit/inserts will be required in that process?

[jondoeuk]

Ultimately, the company aims to move to iPSC-derived CAR-T cells as well, but its effort in this area is still at an early stage https://www.nature.com/articles/d41587-021-00027-1

They are also working on iPSC-derived CAR-NK cell therapies as well.

[OldAIMGuy]

I let 5% of my shares go today at $59.95 for a short term gain.
Next -5% Sell Target = $63.12
Next +12% Buy Target = $46.47
Best wishes,
OAG

[jondoeuk]

The company will host an innovation day focused on early R&D on Tuesday, June 21 at 2:00 PM ET. It will focus on the company's gene engineering platform technologies, novel approach to cell and gene therapy, and emerging discovery programs.

[OldAIMGuy]

I added CRSP as a new position at $51.27 at the start of May.

Best wishes,
OAG

[jondoeuk]

Speaking of anti-CD70 CAR-T's https://www.sciencedirect.com/science/article/abs/pii/S153561082200157X

[jondoeuk]

EHA PR https://www.globenewswire.com/news-release/2022/05/12/2442178/0/en/CRISPR-Therapeutics-Announces-Oral-Presentation-of-New-Clinical-Data-on-Anti-CD70-Allogeneic-CAR-T-Therapy-CTX130-for-Patients-with-T-cell-Lymphoma-at-the-Annual-European-Hematolog.html

[jondoeuk]

As for edits, knockouts (in addition to CD70) could include TET2 [1], CD95 [2], TGFBR2 [3], regnase-1 [4], and/or SOCS1 [5]. Also, the knock-in of (inducible) IL-12 [6-8].

Refs:
1 https://www.nature.com/articles/s41586-018-0178-z
2 https://www.jci.org/articles/view/121491
3 https://insight.jci.org/articles/view/133977
4 https://www.nature.com/articles/s41586-019-1821-z
5 https://www.science.org/doi/10.1126/sciimmunol.abe8219
6 https://aacrjournals.org/cancerres/article/71/17/5697/568127/IL-12-Release-by-Engineered-T-Cells-Expressing
7 https://www.tandfonline.com/doi/full/10.4161/2162402X.2014.994446
8 https://www.cell.com/molecular-therapy-family/oncolytics/fulltext/S2372-7705(17)30052-9

[jondoeuk]

They are also working with NKTX on three different products. One will combine CAR-NK plus CAR-T (both could target two different antigens), as well as two CAR-NK cell products, one of which will target CD70 https://crisprtx.gcs-web.com/static-files/83035e80-926a-4e61-b167-bfcde6392ee6

[jondoeuk]

The company hopes to have an R&D Day mid-year, with a pipeline update for its regenerative med and in vivo approaches, as well as additional info.

[JJ8]

My day order to buy CRSP at $65.40 was filled. Cheers & GLTA

PS: I jumped in small this dip. But I plan to buy more if it dips lower!

[jondoeuk]

The company has expanded the CTX110 trial to incorporate consolidation dosing and begun treating patients in a pivotal arm. Also, top-line data is expected to be reported this half for the ongoing CTX120 and CTX130 (in ccRCC and T/B-cell malignancies) trials.

In addition, they have locked in the design and edits (four or five) for next-gen. Now, are designing third-gen, which will have seven or eight edits. Beyond that, with their own facility, have automated parts of manufacturing, are using machine learning plus translational data, as well as CRISPR screens. Preclinical data from last year https://aacrjournals.org/cancerres/article-abstract/81/13_Supplement/1537/667455/Abstract-1537-CD70-knockout-A-novel-approach-to