Idera Pharmaceuticals: Phase III Melanoma Trial Data Is Expected Any Time , Enter Now Exponential Upside Possible
Seeking Alpha Analyst Since 2014
Summary
- Huge upside possible very soon based on the potential of upcoming Phase-3 data Expected in March 2021 (RSI <38-oversold), Small float ~38m.
- Bakers Brothers holds ~4.6m shares and Pillar Pharmaceuticals holds ~ 18.5m shares.
- Last Dec. CEO has decided to take shares as his one year of salary instead of cash i.e. (worth >500k).
- Ph-3 data of advanced anti-PD-1 refractory melanoma expected anytime in this quarter. Total market in the US & EU together is ~1B but currently IDRA trading at ~200m Valuation.
- Europe partnership news for the anti-PD-1 refractory melanoma expected anytime.
Summary contd..
· FDA granted Orphan designation and company is preparing for the accelerated approval
· Enough cash in hand until Q1 of 2022 and current float is only 38m
· ~ 140m additional Private placement from two of the largest investors (BB and Pillar investment) in place for the product launch soon after the FDA approval
· Company may enter into multiple solid tumors trials soon after successful Ph-3 data and will make a major difference in converting Cold tumors into HOT
· MSS-CRC ph-2 data expected in Q3 2021
· Collaboration with AbbVie for Head & Neck data expected anytime
· Pancreatic trial already in progress
· IMO-2125 Ipi and Nivo in Patients with Advanced Cancers (PRIMO) already in progress
· IMO-2125 in Pathological Tumor Stage (P) T3-4 cN0M0 Melanoma (INTRIM) already in progress
· Most advanced and undervalued ph-3 TLR-9 company which is about to bring out the product into the market, compare to other TLR 9 companies which are having MC of >300m with only ph1/ph2
· To get more information read the CEO’s 2021 JP Morgan Conference presentation. https://ir.iderapharma.com/static-files/b5280619-415a-4fa8-8e39-b6245bfbf8b7
Reasons to Believe that the Illuminate Phase-3 will be a grand success
Here are the key reasons to Believe that the Illuminate Phase-3 will be a grand success :
1. Historical data of 321 patients suggest ipilimumab mono-therapy ORR of 9.5% and DCR of 28.7% VS IDRA's ORR of 22.4% and 71.4% DCR from Phase-2 trials indicates the success chances of Phase-3 .
2. IDRA's Phase-1 patients of 8MG dose became part of the total count of Phase2 patients .As per the initial Phase-1 trial design by IDRA and MD Anderson, they had opened up to all types of patients , including ECOG-level2 whose life expectancy is less than a month, to understand who all may benefit from TILSO + ipi combination based on the translation data gathered from series of biopsies .This trial design was mainly recommended by Dr. Adi Diab's team from MD Anderson . Both Phase 1 And Phase-2 trials were very heavy in Biopsies to double confirm the hypothesis and the results were confirmed By the same reputed Dr. Adi Diab and his team in ASCO conference meeting. Reputed doctors from MD Anderson Will not play with their patients life if they didn’t have enough proof that TILSO is the solution for the PD-1 failure patients. I believe more than IDRA it is the interest of MD Anderson who wants TILSO to be used for their refractory melanoma patients . Experienced doctors like Dr. Adi Diab can already do the math in their head and tell you what the final expected ORR of Ph3 will look like. And Dr. Adi Diab mentioned in one of the conference call that he expects the final phase-3 ORR will be north of 30%. And you can Imagine what will happen to this tiny company if Dr. Adi Diab is right.
3. As state above because of including all kind of phase 1 patients into phase 2 trials, the ORR took a hit and came down drastically to 22% . There were many patients who were so sick that they couldn't even make to the 2nd dose of TILSO and of course they will not respond but unfortunately those patients will counted towards the total number of patients for the ORR calculation. If you are comparing phase-2 ORR to determine the the outcome of phase-3 ORR then you are making a huge mistake, as this trial has been designed bit differently than other cancer trials. Vin and team always wants to make 200% sure that TILSO is actually working than shooting in the dark before stepping forwards towards phase 3. MD Anderson’s head of the Melanoma department executives used to take special interest in attending Illuminate 204 meeting and there must be a reason for their believe and interest in TILSO.
4. Most important Takeaway: After learning a lot from the translation data taken from the numerous biopsies, scientist in the company and MD Anderson doctors made the deterministic conclusion as to who will most likely be the responder for the TILSO and ipi combo. Hence the patients “Inclusion” criteria for phase-3 has been altered accordingly to make more stricter than the phase 2. Example, The ECOG level-2 patients are excluded from the phase-3 trial. Of course the phase 3 ORR must be much higher than phase 2 ORR if TILSO is doing what it is so far showing through the translation data given out by the company in various presentations in multiple Medical conferences.Having said that I will not be surprised if the final ORR of Ph-3 is north of 30%
5. Illuminate Phase-3 is a Blinded study but the clinicians and doctors know which patients is getting which drug ( ipi alone vs ipi + tilso combo). Have you ever heard of any cancer trial closing six months ahead of the original schedule ? It is always the other way around. Does it make you think that why doctors and clinicians were so eager to put their patients into the Illuminate phase-3 trial vs. so many other similar type of trials ? The reason is very simple : They want to illuminate their patients life who are in desperate need. Not Considering the COVID situation.
6. If you recall from the past medical conferences , IDRA has presented the translation data which also proved the point that patient who didn’t respond to ipi alone after PD1 failure, was able to respond with the TILSO + IPI combo. What does that sound to you when you have doubts of TILSO success ? TILSO is able to overcome ipi resistance as well. Huge..isn't it ? Time will tell..
7. Could you guess why company has moved two out of three IST studies as the registered studies under the clinicaltrials.gov after running these three studies independently for more than a year + ? Reason is simple, company decided to make it official so that the result from these trials can be considered towards FDA approvals for other Solid tumors types. Yes, I am referring the below two studies:
1. A Randomized Controlled Phase II Trial With Intradermal IMO-2125 in Pathological Tumor Stage (P) T3-4 cN0M0 Melanoma (INTRIM)
A Randomized Controlled Phase II Trial With Intradermal IMO-2125 in Pathological Tumor Stage (P) T3-4 cN0M0 Melanoma - Full Text View - ClinicalTrials.gov
2. Intratumoral Tilsotolimod, a TLR-9 Agonist, Together With Intratumoral Ipilimumab and Intravenous Nivolumab in Patients With Advanced Cancers (PRIMO)
Company PR: https://www.globenewswire.com/news-release/2018/04/16/1471878/0/en/Idera-Pharmaceuticals-Enters-into-a-Clinical-Development-Support-Agreement-with-Pillar-Partners-Foundation-to- Expand-the-Clinical-Research-on-IMO-2125-beyond-PD-1-Refractory-Melano.html
8. Remind you all that company has started a registered trial for Pancreatic Cancer after seeing the activity in IMO-2125 Mono trial but never announced via PR.
PANFIRE-3 Trial: Assessing Safety and Efficacy of Irreversible Electroporation (IRE) + Nivolumab + CpG for Metastatic Pancreatic Cancer
PANFIRE-3 Trial: Assessing Safety and Efficacy of Irreversible Electroporation (IRE) + Nivolumab + CpG for Metastatic Pancreatic Cancer - Full Text View - ClinicalTrials.gov
9. Imagine When all of these behind the scene trials will start feeding the positive results??? Place your bets accordingly.
10. Illuminate Phase-3 trial was in such high demand by the medical professionals that they had to take way more patients than what they officially Targeted for and announced to the outside world.
FUTURE OF IDRA’s TLR-9 IMO-2125 (Tilsotolimod)
MODTYLSO will be shown in 301 to reverse resistance to PD1 in melanoma. That is around 10K patients annually. A blinded controlled phase 3 with blockbuster results in refractory melanoma from a drug that already has a Fast-Track designation from the FDA will likely garner an Accelerated Approval designation and put MODTYLSO on the way to market. Then comes the resistance to PD1 in other indications. This is will create a tsunami of interest in the oncology world where 87% of all cancer patients become resistant to PD1. MODTYLSO and 301 is a likely a game changer.
Timing is everything. Between March and Sept 2021 Idera would report the results of Tilso in refractory melanoma and refractory solid tumors opening the way for sales in 2022 and pivotal registration studies in several solid tumors. These are all markets in the billions. No meaningful alternatives. Tilso is not the most advanced Tlr9 molecule but the only molecule advancing to market in PD1 refractory tumors. An incredible year ahead.
Market caps do not predict outcomes. Patients do. Idera at $4 per share or $5 per share is irrelevant as well as any share price behavior before the results of 301. I can assure you a rally to $10 per share will not affect the outcome nor the future value. Accelerated Approval Designation by the FDA of MODTYLSO as predicted by the company management would impact value.
The data will create its own logic with results that can be transformative for patients who are resistant to PD1 therapy. This is a $50b market with melanoma resistant being $1B. This is one of the first fully randomized blinded studies of an IO drug response as opposed to an agent that can overcome resistance. The results of illuminate 301 will change the dynamics of the IO market. As for the wall street apathy I compare it to the time Wall Street bough that IDO agonists can solve the resistant phenomena and took the value of Incyte to $35B before Incyte suspended the phase 3 trials for IDO and crashed to $7B. Wall Street makes mistakes and sometimes the mistakes are BIG.
Mr. Milano who guided the company into completing a a phase 3 registration randomized study in 481 PD11 refractory melanoma patients stated that the market for this indication is $1B with no competition. He stated that they are working closely with BMS to address the unmet need in the entirety of the PD1 refractory market whose size is many multiples of the first indication. Milano’s leadership is not in vain. He took Viropharma from a worse place to an acquisition of $5B by shire. He maintained the momentum of Tilsotolimod against all odds including funding the company through Q1 2022. Milano expressed his belief that the Tilsotolimod will prove efficacious in testing the PD1 refractory patients. The only competition I see is Iovance whose value is $6B and whose cost is about a $1M per patient. Illuminate 301 positive results will not move the price by a needle. It will be a tsunami.
Tilso has completed recruitment of patients in early March 2020 in less than 22 months from starting the phase 3. Tilso has orphan and fast track designations and is few days away from the read out. The management increased the number of patients from 308 to 481 in August 2019 to increase the probability of success. All of this increases the chance that Tilso will become standard of care at least 2 years ahead of other players including Checkmate which is having much higher MC than IDRA. Idera has the confidence of BMS with free supply of drug. They have the confidence of abbvie with the Tilso combination with AbbVie drugs. Have the confidence of two investigators in Amsterdam and Paris. It seems pharma and clinicians like Tilso and the management. Wall Street makes mistakes. And when they do it is colossal. Remember incyte and IDO. I would rather go with management has good relations with pharma and clinicians than with analysts. Wall street does not make drugs clinicians do. The mistake that idera did was the failed merger with Biocryst that blew up the value and since then it has been a big challenge to manage and that is where Vin succeeded to overcome that mistake with a robust pipeline.
There is nothing more to add to the Tlr9 science other than driving a tlr9 product into the market. That is what Milano has shown his competence in. With five clinical trials on going in refractory melanoma, MSS-CRC, head and neck, melanoma vaccination and other tumor types, in combination with four other drugs, in collaboration with 2 large pharma companies, tilsotolimod is the most advanced tlr9 drug and the most applied in the Resistant IO space. That is where Milano took Idera. The recently awarded patents for the combinations of Tilsotolimod with other IO drugs in many tumors created a formidable barrier to entry by other players, including the company ex. Checkmate Pharma.
Nowhere is quite somewhere when you consider the facts that somehow escapes the attention of the smart players. 1- A randomized phase 3 trial in PD1 resistant melanoma patients of Tilso plus IPI in collaboration with BMS that will read out in q1 2021. 2- A single arm phase 2 trial in 20 metastatic MSS-CRC non responders to IO drugs in a triple combination in collaboration with BMS. 3- a 70 PD1 resistant head and neck patient in a quadruple combination with AbbVie drugs 4- another French sponsored study of a triplet combining Tilso with IPI and NVivo in collaboration with BMS in PD1 resistant solid tumor patients. It seems to me that Tilso could soon be the go-to drug in the PD1 resistant market. That is an estimated $25B market. That is somewhere.
IDRA Ongoing Trials:
1)A Study of IMO-2125 in Combination With Ipilimumab Versus Ipilimumab Alone in Subjects With Anti-PD-1 Refractory Melanoma (ILLUMINATE-301) (ILLUMINATE-301)
https://clinicaltrials.gov/ct2/show/NCT03445533?term=idera+pharmaceuticals&draw=2&rank=4
2) Study of Tilsotolimod in Combination With Nivolumab and Ipilimumab for the Treatment of Solid Tumors (ILLUMINATE-206)
https://clinicaltrials.gov/ct2/show/NCT03865082?term=Tilsotolimod&draw=2&rank=1
3)A Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-368 Plus Tilsotolimod and Other Therapy Combinations in Participants With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
https://clinicaltrials.gov/ct2/show/NCT04196283?term=Tilsotolimod&draw=2&rank=2
4)A Randomized Controlled Phase II Trial With Intradermal IMO-2125 in Pathological Tumor Stage (P) T3-4 cN0M0 Melanoma (INTRIM)
5)Intratumoral Tilsotolimod, a TLR-9 Agonist, Together With Intratumoral Ipilimumab and Intravenous Nivolumab in Patients With Advanced Cancers (PRIMO)
6)PANFIRE-3 Trial: Assessing Safety and Efficacy of Irreversible Electroporation (IRE) + Nivolumab + CpG for Metastatic Pancreatic Cancer ***NEW TRIAL***
PANFIRE-3 Trial: Assessing Safety and Efficacy of Irreversible Electroporation (IRE) + Nivolumab + CpG for Metastatic Pancreatic Cancer - Full Text View - ClinicalTrials.gov
Disclosure: I wrote this article myself, and it expresses my own opinions. All the contents are based on my sole understanding of the company and their lead candidate. Please do your own research before making any investment decision.
Analyst's Disclosure: I am/we are long IDRA.
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