Korro Bio, Inc. (NASDAQ:KRRO) is a biotech that is working on advancing its RNA editing platform OPERA to treat certain types of disorders. The first RNA edited oligonucleotide drug of its kind from this technology platform is known as KRRO-110. This specific drug is being used to target patients with a rare liver disorder known as alpha-1 antitrypsin deficiency [AATD]. The important thing to note here is that there are two possible catalysts for investors to look forward to regarding this company.
The first of which is that it expects to initiate its first-in-human [FIH] study, using KRRO-110 for the treatment of these patients, in the 2nd half of 2024. From there, it is expected that interim results could be released from this very same phase 1/2 study in the 2nd half of 2025. Should the use of its OPERA technology program pan out, then it is expected that it could go after two other large target market indications, which are Parkinson’s Disease [PD] and amyotrophic lateral sclerosis [ALS]. The ability for it to expand its technology is highly ideal and could be utilized to eventually help many patients with limited options.
KRRO-110 For The Treatment Of Patients With Alpha-1 Antitrypsin Deficiency
As I stated above, the goal of Korro Bio is to advance the use of KRRO-110 for the treatment of patients with Alpha-1 Antitrypsin Deficiency [AATD]. The use of this drug for the treatment of this patient population is expected to be explored in a first-in-human phase 1/2 study. Such a trial is not expected to be initiated until some point during the 2nd half of 2024. This will be one milestone for investors to look forward to.
Before going over another catalyst to come about from this program, it is first important to understand what AATD is and what the possible market opportunity for it could be. Alpha-1 Antitrypsin Deficiency [AATD] is a type of disorder characterized as a liver and/or lung disorder where there are little to no levels of Alpha-1 Antitrypsin [AAT] proteins in the blood. Why is this a bad thing? Well, the liver releases AAT to protect the lungs so no damage occurs. With no AAT being produced, the lungs can become damaged, leading to a host of symptoms. In terms of the liver, AAT gets stuck in there and causes damage as well.
There are several symptoms that patients with AATD experience, and they are as follows:
- Constant respiratory infections
- Fatigue
- Vision problems
- Unintentional weight loss
- Rapid heartbeat.
The truth is that this specific indication offers the company the ability to target a considerable market opportunity. It is expected that the global alpha-1 antitrypsin deficiency treatment market size is expected to reach $2.6 billion by 2027.
This is a huge market opportunity. However, it is important to note that this company is specifically targeting the PiZ mutation. The thing with this disorder is that a mutation in the SERPINA-1 gene causes no AAT protein to be produced. However, in the case of the PiZ mutation type, these patients would be more susceptible to emphysema and liver disease. This is not a big deal because it is said that >95% of AATD patients have this PiZ mutation type.
The other catalyst that investors can expect would be the release of interim results from the soon-to-be initiated phase 1/2 study using KRRO-110 for the treatment of patients with Alpha-1 Antitrypsin deficiency [AATD]. Such data is expected to be released in the 2nd half of 2025. The company thus far has been able to release some pretty good preclinical data showing that its RNA oligonucleotide is capable of being able to efficiently produce 50µM of functional AAT protein after only a single dose in a preclinical mouse model. If the ability to generate this much AAT protein can be replicated in a phase 2 study in humans, then it could be a very useful and possibly best-in-class drug.
Financials
According to the 10-Q SEC Filing, Korro Bio had cash and cash equivalents of $138.8 million as of March 31, 2024. However, after this reported quarter, it entered into a PIPE financing agreement with new and existing accredited investors. This was done to sell an aggregate of 1,249,283 shares of its common stock in a private placement [PIPE] that helped it to raise approximately $70 million in gross proceeds. This brings about pro forma cash of $236 million before fees and expenses.
The bottom line is that this company now has enough cash on hand, given a quarterly cash burn of about $20 million, for a cash runway to fund its operations into the 2nd half of 2026. This will be plenty of time to make it through the interim analysis of the first-in-human phase 2 study of KRRO-110 for the treatment of patients with AATD. Plus, it might even be enough for full trial completion, expected in 2026.
Risks To Business
There are several risks that investors should be aware of before investing in Korro Bio. The first risk to consider would be regarding the advancement of KRRO-110 for the treatment of patients with the soon-to-be initiated phase 1/2 first-in-human study for the treatment of patients with AATD. Even though preclinical animal model testing showed a sharp increase of 50µM Serum AAT protein, to reduce disease, there is no assurance that a similar or superior elevation of this protein will be observed in humans. Nor, that the primary efficacy measure is going to eventually be met with statistical significance.
The second risk would be the advancement of its RNA editing technology platform known as “Oligonucleotide Promoted Editing of RNA” or OPERA. That’s because the belief is that by using this RNA editing technology, it could alter the course of disease with several enhancements over other gene therapies and gene editing technologies. What could be possible with OPERA over other such technologies would be the ability for repeat dosing, minimal risk of off-target effects, edit RNA without altering the genome in any way. The risk here is that there is no assurance that this technology will be proven in humans. Nor that it will be able to accomplish its intended goals of being superior over other gene and gene editing therapies.
The third and final risk to consider would be regarding the development of its other OPERA therapies in its pipeline. It is using one OPERA drug to target the LRRK2 protein for the treatment of patients with Parkinson’s Disease [PD] and then another one to target the TD43 protein for the treatment of patients with amyotrophic lateral sclerosis [ALS].
One thing to note is that KRRO-110 and the targeting of the LRRK2 protein for PD are to repair a mutation, while the goal of targeting TDP43 is to disrupt aggregation [build up] of the molecule. These are still in preclinical testing, but there is no assurance that either of these other RNA edited drugs will achieve success in a phase 1trial for human testing. Nor, that the data will be solid enough to move to the next stage of clinical testing.
Conclusion
Korro Bio has done well to advance the use of its RNA editing OPERA platform for the treatment of patients with Alpha-1 Antitrypsin Deficiency [AATD]. The goal is to get a regulatory filing through so that it could begin a first-in-human study of KRRO-110 to treat this specific patient population in the 2nd half of 2024. From there, it will not be long before investors can get a glimpse of data from this mid-stage study. That’s because it is expected that an interim analysis of this phase 1/2 first-in-human study, using this drug to treat these AATD patients, will be released by the 2nd half of 2025. With a full analysis of this very same data to be released in 2026.
Positive data here would not only mean the ability for this company to tap into this large $2.6 billion market opportunity for these patients in 2027, but it would also give credibility that its OPERA platform is capable of altering RNA genome effectively.
This would then open the door to easily advance the use of this technology platform towards some other indications I noted directly above, like the targeting of patients with Parkinson’s Disease [PD] and amyotrophic lateral sclerosis [ALS]. The amyotrophic lateral sclerosis market is expected to reach $1.33 billion by 2033. Then, the other market is an even larger opportunity for this biotech to go after. It is expected that the global Parkinson’s Disease drugs market size is projected to reach $10.4 billion by 2031. With an interim analysis of the phase 1/2 study of KRRO-110 to target AATD patients in the 2nd half of 2025, plus the ability to expand the use of its technology towards patients with PD and ALS, I believe that investors could benefit with any potential gains made.
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