There are many ways to think about partnering

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LWS
Posts: 142
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Sun Feb 06, 2022 4:01 pm

AbbVie already a partner (Looks like an outstanding combination, preclinical)

***Results: A dose-dependent synergistic activity in inducing apoptosis was observed in multiple AML cell lines when combining imetelstat with venetoclax. In the MOLM-13 cell line, single-agent imetelstat and venetoclax had modest apoptotic activity after 48 hours (22% and 30% respectively), but the combination achieved 88% at 48 hours and nearly 100% at 96 hours. ****
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"NORTH CHICAGO, Ill., Nov. 21, 2018 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to VENCLEXTA® (venetoclax tablets) in combination with azacitidine, or decitabine, or low-dose cytarabine (LDAC) for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. This indication is approved under accelerated approval based on response rates. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials."
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Geron is planning to investigate Imetelstat combinations on the clinical level, having proved that the medicine is safe and effective as a single agent. To do so they must partner on some level with a company that owns an approved cancer medicine. The preclinical combination (Imetelstat & Venclexta) has shown outstanding results. This will likely be the first successful Imetelstat combination.
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Experimental and Molecular Therapeutics
Abstract 1101: Telomerase inhibitor imetelstat in combination with the BCL-2 inhibitor venetoclax enhances apoptosis in vitro and increases survival in vivo in acute myeloid leukemia

Joshua J. Rusbuldt, Leopoldo Luistro, Diana Chin, Melissa Smith, Amy Wong, Margarita Romero, Aleksandra Rizo, Jacqueline Bussolari, Fei Huang and Amy (Kate) Sasser
DOI: 10.1158/1538-7445.AM2017-1101 Published July 2017

ArticleInfo & Metrics
Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC

Results: A dose-dependent synergistic activity in inducing apoptosis was observed in multiple AML cell lines when combining imetelstat with venetoclax. In the MOLM-13 cell line, single-agent imetelstat and venetoclax had modest apoptotic activity after 48 hours (22% and 30% respectively), but the combination achieved 88% at 48 hours and nearly 100% at 96 hours. Similarly enhanced apoptotic activity was also observed in PBMCs purified from 4 AML patient whole blood samples. Molecular analyses showed combining imetelstat with venetoclax reduced hTERT expression and telomerase activity much more strongly than either agent alone. Furthermore, in vivo studies showed all mice tolerated the combination of imetelstat with ABT-199 well, with increased life span as compared to the vehicle control (68.1%, p=0.0001), to imetelstat (39.6%, p=0.0011) alone, or to venetoclax (23.3%, p=0.0001) alone. In the combination group, 40% of treated mice were alive 77-days after treatment discontinued whereas all mice of the other single agent arms died within two weeks, demonstrating a significant survival benefit.

kmall
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Re: There are many ways to think about partnering

Post by kmall » Mon Feb 07, 2022 6:34 pm

Here's our answer on whether the UK MHRA application for MAA has been initiated with the announcement on 10/25/2021 of ILAP Innovation Passport or IF a formal application still needs to be submitted........as suspected......

RE: MHRA / Imetelstat (CSC ID 87040)
MHRA Customer Services - 11:51am

Dear Kmall,

Thank you for your email. I am afraid we are not able to release any information about whether an application has been submitted or its progress to anyone other than the marketing authorisation holder.

Kind regards,

C****
MHRA Customer Experience Centre
Communications and engagement team
Medicines and Healthcare products Regulatory Agency
10 South Colonnade, Canary Wharf, London E14 4PU

**So as I suspected from the start NO ONE here knows for certain where we stand until we get CLARIFICATION from GERON directly.
This entry is in this thread since it was posted earlier here about a timeframe on where we stand. -Kmall

LWS
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Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Sat Feb 12, 2022 7:19 pm

(Previous)--The most important topic and only topic is Imetelstat, that can be broken down:

1. Effectiveness and safety as a single agent (phase 2 successes and ongoing phase 3)
2. Potential in combinations (blood cancers and solid tumor cancers)
3. Collaborators (MD Anderson)
4. Potential partners (Novartis, JNJ, BMY, AbbVie, etc.)
5. Approvals (England (rolling data), USA, European Union)

We all know that Geron's PPS (for whatever reason) is ridiculously low. We also know that there will be an EVENT (more than one), that will drive the PPS upward.
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(Update)--There is every indication that phase 3s are continuing to supply good (safe, effective, proven, needed, remarkable, compelling--meeting all criteria) rolling-data that are continuing the phase 2's successes. That should be all that is needed now, for MHRA (MAA--Marketing Authorization Application, ILAP---Innovative Licensing and Access Pathway) approvals, based upon rolling and continuous data from phase 3, and supplemented with data from MD Anderson.

It could all come at once (in February or March, I believe) -- accelerated approvals, new partners, AbbVie (AML) combination trials. AbbVie is already a partner of record, but to what degree? This is the EVENT that patients, partners and investors are waiting for. Logic (not always valid) indicates the MAA is well underway, but there are uncertainties.
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TELOMERE [Imetelstat (Geron) & Venetoclax (AbbVie)]

TELOMERE: Planned Phase 1/2 Investigator-Sponsored Clinical Trial in Relapsed/Refractory Acute Myeloid Leukemia

TELOMERE is a Phase 1/2 clinical trial planned to evaluate imetelstat in patients with relapsed/refractory acute myeloid leukemia, or AML. The trial is designed to test two distinct combinations of imetelstat and venetoclax or imetelstat and azacitidine. The primary objective of the Phase 1 portion is to identify the safe dose of each of the combinations. Up to 20 patients are expected to be enrolled into this portion of the TELOMERE study.

The primary objective of the Phase 2 portion of the study is overall response rate for each of the combination regimens. We expect the trial to start in the first half of 2022.

LWS
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Re: There are many ways to think about partnering

Post by LWS » Thu Feb 17, 2022 7:14 pm

Follow-up: That should be all that is needed now, for MHRA (MAA--Marketing Authorization Application, ILAP---Innovative Licensing and Access Pathway) approvals, based upon rolling and continuous data from phase 3, and supplemented with data from MD Anderson.
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It has been very quiet. We still do not know the MAA status, but commonsense and logic would indicate that MAA has been applied for as a necessary ingredient for accelerated MHRA (UK) approvals. There is ample positive data from phase 2 (completed trials) and phase 3 (ongoing trials) with Imetelstat as a single agent now.

In addition, MD Anderson has only had positive comments, as they continue their use of Imetelstat for treatment and research. Also, AbbVie would not be entering the TELOMERE combination trials, without a very high degree of likely successes. I suspect that there have been some 'under-the-radar' clinical studies, with very good results.

biopearl123
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Re: There are many ways to think about partnering

Post by biopearl123 » Thu Feb 17, 2022 11:23 pm

LWS, as a reminder and for the sake of clarity, no PIII data is available now and won’t be until the first PIII study in MDS is unblinded. That occurs one year after the last patient was enrolled, I think last October or November. Then the data is analyzed and is expected to be released in Jan of 2023. Until then it is not known to regulators. Regards, bp

LWS
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Re: There are many ways to think about partnering

Post by LWS » Fri Feb 18, 2022 4:49 am

biopearl123--(for discussion) --MHRA & UK accelerated approvals (MAA--Marketing Authorization Application, ILAP---Innovative Licensing and Access Pathway)

I have little knowledge here. I thought the MHRA (UK) process was put in place to get around some traditional roadblocks.

A double-blind study means that the patient and the researcher (doctor or scientist) has no knowledge of who is getting the medicine of interest and who is not. However, someone has an overview of the whole process, and sometimes trials are stopped early for compassionate reasons, or overwhelming successes (remarkable & compelling says Dr. Rizo). I don’t have any good examples, at the moment, but I believe (and have heard) they exist.

Looking for examples.

biopearl123
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Re: There are many ways to think about partnering

Post by biopearl123 » Fri Feb 18, 2022 6:49 am

If the UK made a decision in the near future it would be based on current PII data that has been published. That is not impossible as the PII data is strong but perhaps not what the agencies require. A PIV post approval study might be required if that happened or after the PIII data is revealed a conditional approval could be confirmed or rescinded. We have asked Dr Rizo specifically about an early look at the data for the MDS trial (it is built into the MF trial protocol with a pre specified number of deaths trigger). Dr. Rizo was clear, no early look planned for the MDS trial especially since we are now on a short timeline anyway. Yes in some cases the DSMB can make recommendations but the study design seems to point to completion time as planned, especially with the three month shortening of study timeline outlined previously. In any case it is highly unlikely anyone (beside the DSMB) especially regulators have seen any PIII data and can not use this data yet to support approval.

LWS
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Re: There are many ways to think about partnering

Post by LWS » Sun Feb 20, 2022 7:34 pm

(To biopearl123, thanks for the follow-up) ----data safety monitoring board (DSMB)

“The DSMB (data and safety monitoring board), is an independent group of scientists and concerned community members who oversee the interim findings of a research project to determine whether the research undertaken is proceeding without evidence of harm to the subjects enrolled in the study.”

This is my introduction to the DSMB. They exist but are not likely to be a factor here, as you see it. You are probably correct.

Still, as you say, Phase II results were very successful. Also, I believe, MD Anderson can supply additional data. I see no reason why MHRA/UK accelerated approvals (MAA--Marketing Authorization Application, ILAP---Innovative Licensing and Access Pathway) should not be sought. This seems to be in everyone’s interest (patients, Geron staff, investors, potential partners). Still, no one can get inside John Scarlett’s head, but logic and commonsense would favor that he would do everything feasible to get MHRA (UK) accelerated approvals as soon as possible.

FC4364
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Re: There are many ways to think about partnering

Post by FC4364 » Mon Feb 21, 2022 9:27 pm

It makes no sense to apply for ILAP, receive it and then just sit and wait for Father Time to do the heavy lifting. If GERN applied for ILAP, then the intention is to pursue early approval. Matters not if they have yet applied for MA. Processes associated with ILAP will need to be observed first. Now, if the folks in UK responsible for ILAP see what they are looking for in trial results, then early approval is on the table and at such time, GERN is legally responsible for informing investing public that an application has been submitted. I believe GERN will not file FOR Ma until they have been notified by UK authorities that approval is theirs through the ILAP process. After this event from ILAP authorities GERN will file because they are assured of approval. Simply, why file for ILAP and then go through the process if you do not intend to use it? In My Opinion, of course.

LWS
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Re: There are many ways to think about partnering

Post by LWS » Sun Feb 27, 2022 7:09 pm

(Timeline still unknown) ---Geron has always been a long-term speculation and EVENT driven, made longer by the JNJ confusions. Patient's interest should always be first, with investor's interest very important, but secondary. Imetelstat appears very successful now with all the positive trial data, ongoing trials, new trials including combinations & strategic partners (like AbbVie), MD Anderson as a collaborator and pending MHRA approvals. JS and Dr. Rizo clearly have a plan with partners and collaborators, but the details are closely held for now. Something has got to give soon.

LWS
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Re: There are many ways to think about partnering

Post by LWS » Sun Mar 06, 2022 3:55 pm

The Cancer Moonshot & Partners

Unfortunately, we are now dealing with 4 crises in Ukraine simultaneously: war atrocities, famine, disease (possible new COVID mutations), and nuclear weapons in all forms.

The Cancer Moonshot is now back on the table with Imetelstat in the perfect position for MHRA approvals, MD Anderson endorsements, and new combination partners (in addition to AbbVie & AML). The phenomenal phase 2 single-agent successes ("compelling & remarkable") and the ongoing phase 3 confirming trials should bring good news and new partners in the near future.

LWS
Posts: 142
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Re: There are many ways to think about partnering

Post by LWS » Fri Mar 11, 2022 4:37 am

As Covid problems seem to be coming under control, the Ukrainian hot war with all of the implications of war atrocities, chemical & biological weapons and a variety of nuclear (weapon, energy and radiation) problems confront us. The world situation now affects everyone.

Here are some excerpts from the YMB that indicate that all is going well with Imetelstat in trials and in developing partners.
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Geron has raised ~$140 million through a public offering, taken out a loan (in tranches) for $75 million, and hired countless new employees. They also applied for an Innovation Passport in the UK. These actions seem to support the idea that although blinded, management already knows that the trial has hit its primary endpoint. They have all the data they need to see past the patient blinding.

You need look no further than the way they have been using proceeds and their acknowledgment that they will run out of money completely by the first quarter of 2023 (after the Phase 3 is unblinded). There is no contingency plan and they seem unfazed. The quality of people that have been hired don’t seem to be worried that this might be the shortest job on their resume, and instead of cash bonuses this year management has loaded up on stock options. In my opinion it’s all there if you put the pieces together.
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"As a result, and in parallel with our continuing preparations to commercialize imetelstat, we're actively investigating potential relationships with appropriate partners. These include exploration of regional and other deal structures of possible mutual interest, which could potentially further accelerate imetelstat development and commercialization."

LWS
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Re: There are many ways to think about partnering

Post by LWS » Thu Mar 17, 2022 7:32 pm

One form of partner is the collaborator. Mayo Clinic brought Imetelstat to many people's attention a number of years ago ("Tantamount to a Cure"). That position is now occupied by MD Anderson. As far as I can tell, MD Anderson is actively using Imetelstat in trials, treatments and advanced research, with very significant successes. This is extremely important for accelerated approvals such as MHRA (UK), which will use practical considerations, rolling-data, the safety profile and completed trials to form its conclusions.
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From huntingonthebluffs (12/8/21) original post:

Collaborations: Collaboration is a working practice, especially a joint intellectual endeavor between scientists, working together for a common purpose to achieve business benefit. Collaborations consist of two or more entities motivated to solve problems and/or develop solutions, share information, consider alternatives, and engage in advancing knowledge, understanding, solutions, products, organizations, etc. Collaboration relies on openness and knowledge sharing but also some level of focus and accountability on the part of the business organizations.

Scientific Collaborators share our passion and vision. Academic research has an important role throughout the development of new medicines. Our collaborations with many scientific and clinical experts have led to key contributions to the scientific understanding of telomere and telomerase biology, and our telomerase inhibitor, imetelstat. We invite you to partner with us in our quest to develop this novel therapy and make a difference in patients’ lives.

LWS
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Re: There are many ways to think about partnering

Post by LWS » Wed Mar 23, 2022 2:48 pm

This summary of 2021 activities is impressive. Imetelstat (Geron) is on the move. MD Anderson, single-agent, combinations, MHRA (UK) approvals, potential partners and commercialization are all in the spotlight now.
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Thanks to hunter (YMB)---From the proxy,

Our executive compensation program in 2021 was highly influenced by our vision to be recognized as a leader in the treatment of hematologic malignancies and our current plans to develop and potentially commercialize imetelstat, our first-in-class telomerase inhibitor. In furtherance of that vision and those plans, we accomplished the following key activities in 2021:

• Completed patient enrollment in ongoing IMerge Phase 3 clinical trial in lower risk MDS.

• Opened 50% of the total planned clinical sites for IMpactMF, our ongoing Phase 3 clinical trial in MF to facilitate patient enrollment into the trial.

• Presented updated clinical data and analyses from Phase 2 trials of imetelstat in MF and MDS at medical conferences in June and December 2021 that continues to highlight imetelstat’s disease-modification potential.

• Gained access to the new Innovative Licensing and Access Pathway program in the United Kingdom through the receipt of an Innovation Passport for imetelstat to treat lower risk MDS which provides opportunities for frequent interactions with the review staff at the Medicines and Healthcare products Regulatory Agency (“MHRA”) and its partner agencies to discuss imetelstat’s development, regulatory and reimbursement plans in the United Kingdom.

Expanded development pipeline by planning company-sponsored and investigator-led clinical trials in new hematologic indications and treatment combinations designed to broaden imetelstat’s value potential.

• Initiated preclinical research at MD Anderson Cancer Center in lymphoid hematologic malignancies to potentially expand the use of imetelstat beyond myeloid hematologic malignancies.

• Continued discovery research of the potential utility of various compounds as potential next generation oral telomerase inhibitors.

• Achieved targeted organizational growth through hiring of key talent and addition of critical competencies and capabilities, including medical affairs, market access, and Chief Business Officer.

LWS
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Re: There are many ways to think about partnering

Post by LWS » Sun Mar 27, 2022 4:04 pm

This is a good summary as of 3/27/22. Partners and collaborators are in focus now. I suspect some choices have already been made. Imetelstat is a needed, proven medicine.
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from early retirement (YMB)

Notice the more GREAT NEWS that comes out about GERN the more the shorts here bash GERN and the more they sell short sell GERN stock. Shorts are going to lose this game. See below.

1. GERN said March 10, 2022, they (GERN) are now talking to Big Pharma about partnerships! This is HUGE!
2. Big Pharma says they have $1.75 TRILLION yes TRILLION available for making deals biotech companies. This is HUGE!
3. The UK could approve GERN's drug any day now. This is HUGE!
4. Johnson and Johnson insiders are quitting JNJ and running to GERN for employment . Yes JNJ insiders. This is HUGE!
5. GERN's drug is the only drug every to return cancerous bone marrow to normal. This is HUGE!
6. GERN's drug is the only drug to add years of life to the sickest blood cancer patients. This is HUGE!
7. M.D. Anderson and many others are praising GERN's drug online in videos. This is HUGE!
8. M.D. Anderson says that GERN's drug has greatly raised the bar and for the first time ever M.A. Anderson can talk about increasing overall survival (more years to live) of these blood cancer patients. This is HUGE!
9. PCYC ran up 45,000% from these low low levels. GERN's technology blows PCYC drug away. If GERN only goes up 20,000% from here it is still 1 of the best buys of the decade. This is HUGE!
10. On March 11, three stock analyst put strong buys on GERN stock after hearing GERN say they are in talks with big pharma in the March 10 GERN conference call. This is HUGE!
11. 5 stock analyst now have strong buys on GERN with no analyst rating GERN stock a sell. This is HUGE.
12. March 11, 2022 H. C. Wainwright analyst put a $7 dollar 12 month target price on GERN stock after hearing the March 10 GERN presentation.
13. The short sellers have been shorting 330,000 more GERN shares everyday trying to hold GERN's stock price down but these is not going to work. This just winds GERN's stock even tighter for the coming GERN run into the teens. GERN $10 to $20 a share soon!
14. H.C. Wainright is saying GERN stock is going to go up 600% over the next 12 months. This is HUGE!
15. You can buy GERN stock now and make HUGE money or you can listen to the short sellers and take it in the shorts.

realize
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Re: There are many ways to think about partnering

Post by realize » Sun Mar 27, 2022 8:18 pm

Hi LWS,

Please point me/us to the point 1 notes. Did Gern said they are talking to Big Pharma about partnerships on March 10, 2022 ?
I doubt about the point 3 as well. To me it's just another FDA or EU kind of bureaucratic steps which needs to be walked to get approval.

Thanks

LWS
Posts: 142
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Fri Apr 01, 2022 1:16 am

AML is front and center, and AbbVie has a vested interest. The preclinical results are amazing, with a clinical AML combination trial being organized (TELOMERE). How extensive is this AbbVie/Geron partnership?
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From early retirement (YMB)

Published today 3/30 MDPI/Journal of Clinical Medicine. Title: Geron's drug Imetelstat Induces Leukemia Stem Cell Death in Pediatric Acute Myeloid Leukemia Patient-Derived Xenografts.

Concludes: Thus, our data suggest that Geron's drug imetelstat represents an effective therapeutic strategy for pediatric AML.
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(Previous)--AbbVie already a partner (Looks like an outstanding combination, preclinical)

***Results: A dose-dependent synergistic activity in inducing apoptosis was observed in multiple AML cell lines when combining imetelstat with venetoclax. In the MOLM-13 cell line, single-agent imetelstat and venetoclax had modest apoptotic activity after 48 hours (22% and 30% respectively), but the combination achieved 88% at 48 hours and nearly 100% at 96 hours. ****

LWS
Posts: 142
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Sat Apr 02, 2022 4:46 pm

Geron has a renowned collaborator (for research & treatment) with MD Anderson. Their participation is a strong indicator of Imetelstat's successes in many areas.

JNJ and AbbVie will both be present for the long-term. Geron looks like they may have more than one partner, with perhaps a European component (Novartis??). Imetelstat is a proven medicine for single-uses (MF, MDS, PV, ET, etc.) and looks extremely promising for AML (preclinical results & the TELOMERE forming clinical trial) and other blood cancer combinations.

Even in the area of solid cancers there seems to be potential, with the delivery system apparently the problem. Recent papers have shown progress there.

biopearl123
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Re: There are many ways to think about partnering

Post by biopearl123 » Sat Apr 02, 2022 7:08 pm

Caveat superlatives like HUGE. Many a slip twixt the cup and the lip.

LWS
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Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Mon Apr 04, 2022 8:50 pm

I don’t believe there will be a full buyout anytime soon. There is too much promise and potential now.

JS and Dr. Rizo, it appears, plan to stay around for a while. New partners, with very deep pockets, will be chosen, on several different levels—likely more than one partner. Names that come to the surface are AbbVie, JNJ, Novartis, Bristol Meyers.

Mayo Clinic (Tantamount to a cure)
JS (Bigger than all of us)
Dr. Rizo (Remarkable and compelling)
MD Anderson (Numerous positive remarks)

All of the science and completed clinic trials have proven out for Imetelstat, with ongoing, confirming phase 3s in progress. The preclinical testing (especially AML in combinations) has been very impressive. TELOMERE (clinical AML combinations) is just getting underway.

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