It’s All About Common Sense: Intellia Therapeutics

The Nonsensical Downgrading of Development-Stage Firms Like Intellia Therapeutics

It makes no sense to downgrade a development-stage firm such as CRiSPR gene editing IntelliaTherapeutics (NTLA) when only based on stopping short of attaining analysts’ expectations with regard to revenues and incomes. Development-stage firms yet to have products on the market to generate money, contrarily, serious development-stage firms spend millions to realize their goals and put safer and more effective products in the hands of the physicians.

The novel CRiSPR-gene editing is a historical happening, a revolution that made it possible to manipulate DNA and bring to the clinic the dream of miraculous cures.   

Firms such as Intellia should not be evaluated based on counting the increase or the decrease in revenues and incomes, as they have no products anywhere for sale. The revenues mentioned by the evaluators emanate from collaborators and other firms that seek licensing agreements, which have never been steady.      

You cannot downgrade Intellia Therapeutics while it is on the verge of reporting initial data from Phase 1 study of NTLA-2001, a single-course therapy and a potential cure for transthyretin amyloidosis (ATTR).

The firm is also on track to submit an IND, or IND-equivalent, in the next couple of months for NTLA-5001 for acute myeloid leukemia (AML) as well as for NTLA-2002 which aims at curing hereditary angioedema (HAE).    

Whether attaining or not attaining what analysts expect the mere reality is that at the end of 2020 Intellia had in its coffer $597.4 million in cash.  

Intellia Therapeutics is one of the leaders of genome-editing companies. It is focused on developing curative therapeutics using CRISPR/Cas9 technology both in vivo and ex vivo. After reporting its operational highlights, and its financial results for the fourth quarter and year ended December 31, 2020, we loved it more than we did before, rather than downgrading it while it is still building its Empire that we believe will be a historical accomplishment. 

From the President & CEO of Intellia Therapeutics

Intellia Therapeutics President and Chief Executive Officer, John Leonard, M.D., said, “Dosing our first patient with NTLA-2001, the first-ever systemically delivered CRISPR-based therapy, was a major milestone for our team, as we completed our transition to a clinical-stage company in the fourth quarter. Looking ahead, we are focused on our three core priorities for 2021: clinical validation of our approach with NTLA-2001, advancement and expansion of our in vivo and ex vivo pipeline, and continued platform innovation. We have made steady progress in our global Phase 1 study of NTLA-2001 and look forward to sharing our first clinical data this year. Additionally, we are on track to submit first-in-human regulatory applications to begin clinical studies of NTLA-5001 for AML and NTLA-2002 for HAE, and we plan to nominate at least one new development candidate from our research portfolio.”

Intellia Therapeutics Fourth Quarter 2020 Highlights 

NTLA-2001 is the first systemically delivered CRISPR-based therapy dosed in a patient with transthyretin amyloidosis (ATTR) and could potentially be the first curative treatment for ATTR: 

Applying Intellia’s in vivo lipid nanoparticle (LNP) delivery technology, NTLA-2001 offers the possibility of halting and reversing the disease with potent, lifelong transthyretin (TTR) protein reduction after a single course of treatment.

Important to know: NTLA-2001 is part of a co-development/co-promotion agreement between Intellia, the lead party, and Regeneron Pharmaceuticals (REGN).  

Intellia would be reporting good news this year with the interim clinical data from the Phase 1 study, and the results are expected to characterize the emerging safety and activity profile of NTLA-2001 at the initial dose levels.

Intellia’s continuing enrollment of patients in the study and submitting additional regulatory applications in other countries as part of its ongoing, global development strategy is also good news

It is comforting listening to Intellia’s intentions to evaluate NTLA-2001 in a broader ATTR population of both polyneuropathy and cardiomyopathy patients following its Phase 1 safety assessment and dose optimization.

NTLA-5001 for AML 

NTLA-5001 is a potential best-in-class engineered T cell therapy designed to treat all genetic subtypes of AML. This investigational candidate is an autologous T cell receptor (TCR)-T cell therapy targeting the Wilms’ Tumor 1 (WT1) antigen utilizing Intellia’s proprietary cell engineering process.

As mentioned above, we learned that the firm plans to submit, in mid-2021, an Investigational New Drug (IND) application or equivalent regulatory application for NTLA-5001. It is indeed, the first-in-human trial expected to evaluate the safety and activity of NTLA-5001 in patients with persistent or recurrent AML who have previously received first-line therapies. This will be a historical achievement.

Important for us is also learning that NTLA-5001 has demonstrated high anti-tumor activity in proof-of-concept mouse models of acute leukemias. The preclinical data presented at the ASH Annual Meeting in December where it highlighted the faster expansion and superior function of T cells manufactured by Intellia’s proprietary approach versus the standard T cell engineering approaches in current use.

Moreover, Intellia is evaluating the potential of using NTLA-5001 for the treatment of  WT1-positive solid tumors in preclinical studies.

NTLA-2002 for HAE 

NTLA-2002 aims to prevent attacks of HAE after a single course of treatment. Intellia is applying its modular LNP delivery system to develop NTLA-2002 to knock out the KLKB1 gene in the liver to permanently reduce plasma kallikrein activity. This approach is expected to provide continuous suppression of kallikrein activity and eliminate the significant treatment burden associated with currently available therapies for HAE patients.

Intellia commenced clinical manufacturing activities to support the Company’s plans to submit an IND or equivalent regulatory application in the second half of 2021.

The Company is applying insights gained from NTLA-2001 to expedite the clinical development of NTLA-2002. The first-in-human trial is expected to evaluate safety, tolerability and activity in patients with HAE.

Modular Platform and Pipeline Expansion 

Intellia is advancing its modular platform technologies to broaden the in vivo and ex vivo applications of genome editing. The firm is developing capabilities for innovative CRISPR/Cas9-mediated in vivo editing in multiple tissue types, targeted transgene insertion and an allogeneic approach for the development of “off-the-shelf” T cell therapies.

These efforts will support new therapeutic candidates for genetic diseases requiring removal and/or restoration of a protein, and next-generation engineered cell therapies for cancers and auto-immune diseases.

What Else is Intellia Therapeutics Achieving?

  • Demonstrating the modularity of its targeted insertion approach for a second target, in non-human primates, showing insertion of the SERPINA1 gene produced normal levels of human alpha-1 antitrypsin (AAT) after a single administration.

These results were presented at the Alpha-1 Foundation’s 20th Gordon L. Snider Critical Issues Workshop: The Promise of Gene-Based Interventions of Alpha-1 Antitrypsin Deficiency.

  • Advancing multiple genome editing strategies that may treat both lung and liver manifestations of AAT deficiency (AATD), which occur due to mutations in the SERPINA1 gene.
  • Advancing preclinical validation of in vivo hematopoietic stem cell (HSC) genome editing using the Company’s proprietary non-viral delivery systems and CRISPR/Cas9 technology to potentially cure sickle cell disease. (This research is supported by a grant from the Bill & Melinda Gates Foundation.)

Prohost Observations

As we said above, we are not at all interested in the excuses used to downgrade Intellia and many other development-stage biotech firms with solid fundamentals.

Read more about Intellia Therapeutics by clicking here.

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