Please download Executive Summary  & Team Introduction 

A Potential First & Best Treatment for NSCLC Caused by EGFR Exon 20 Insertion mutations

 
Capella Therapeutics is a San Diego based cancer drug company that is seeking $25-30 million to fund clinical trials of its lung cancer drug candidate, LL-191, which treats resistant cancers caused by Exon 20 insertions and rare mutations of EGFR, for which there are no treatments yet approved.  Efficacy vs. a common EGFR exon 20 insertion mutation was better than agents currently in early clinical trials, and with a much better safety profile.  LL-191 also led to tumor remission and survival outcomes in EGFR primary activating nutation (L858R & exon19 del) and primary resistant mutation  (T790M) in lung & metastases in the brain and bone in multiple mouse models.  This agent also can treat other non-EGFR mutations such as HER2 overexpression & mutations, and (partially treat) YES1 overexpression & RET fusion and mutations.

Evidence of differentiation & improvements over other major EGFR drugs such as TAK788 & Tagrisso:

1. Addressing an unmet medical need

Exon 20 insertions (9-14% of all EGFRm) are a new research “hot spot” because there are roughly 60-90k new patients each year, but there is no approved targeted therapy (and only drugs in an early-stage clinical trial).
LL-191 is potentially the best (it shows unusual efficacy) and possibly the 1st solution for exon 20 insertions therapy (because competitors cannot solve the problem of toxicity prevention from using doses high enough to be curative).

2.  Broader Therapy - Reaches more variations of EGFR lung cancer:

Non-classical/rare EGFR mutations, adding up to >12% of EGFR lung cancer patients
Several types of Tagrisso-resistant or Tarceva/Irresa-resistant NSCLC.
Several types of Tagrisso-sensitive or Tarceva/Irresa-sensitive NSCLC

3. Improved Efficacy – LL-191 has shown superior efficacy vs. Tagrisso on cancers:

Most common brain metastases harboring sensitive primary mutations (brain tumor elimination by LL-191 v. reduction by Tagrisso). Nearly doubled survival outcomes vs. Tagrisso.
Ability to treat leptomeningeal metastases to remission.
Tumor elimination and higher disease-free survival rate in bone metastases (60% by LL-191 vs 25% by Tagrisso), with tumor harboring T790M resistant mutation of EGFR.

4.  Less Side Effects – Improved wild-type selectivity, which could translate into better drug safety and patient tolerability than all other competitors in four potential therapeutic fronts:

Exon 20 insertions (frontline or 2nd /3rd line)
Front line therapy of EGFR NSCLC with primary activating mutations
2nd or 3rd line therapy for resistant NSCLC driven by

EGFR T790M mutation
HER2 overexpression
 
Less efficacy-limiting toxicity suggests a potentially wider clinical therapeutic window to tolerate a higher dose for better efficacy in patients with EGFR Exon 20 insertion and other EGFR mutations.

5. LL-191 Appears to have a favorable toxicity profile

In mice (28 Day GLP Study), STD10 has not been reached at a dose as high as 150 mg/kg, where a tumor has been 100% eliminated with no test article-related anatomic pathology findings.
In dog (28 Day GLP Study), the drug-related clinical pathology findings were only seen at the mid and high dose and were reversible after a 28-day recovery period.
The calculated reasonably safe clinical starting dose for our drug: 75 mg

6. IND-ready 

IND Enabling Studies for LL-191 have been completed. Capella plans to file an IND application on Dec 23, 2020.

7. Global IP coverage

Two families of patents (the composition of matter and use) were filed in 2014 as Provisional Applications in the US and entered National Phase in 2017.  Patents were awarded in the US & seven other countries & pending in other countries.

These patents provide global coverage in seven major traditional pharmaceutical markets, plus potential markets in China, India, Russia, and Ukraine.

The patents in both families will protect about 14 years of exclusive sales, with extensions possible after drug approval.
A third family of patents was filed in 2015 (the composition of matter and use) in the US as provisional applications, covering back-up and follow-up compounds. The corresponding centralized application under the Patent Cooperation Treaty was filed in 2016.
New patent application based on the salt form and polymorph of the drug candidate will be pursued to further elongate the protection period of exclusive sales.

For more information please contact Yun Oliver Long, CEO   YunLong@capellatherapeutics.com