ADCOM

[LWS]

Fireside chats, ASH2023, ODAC

Stifel 2023 Healthcare Conference
Tuesday, November 14th at 9:10 a.m. ET (Fireside Chat)

6th Annual Evercore ISI HealthCONx Conference
Wednesday, November 29th at 10:50 a.m. ET (Fireside Chat)
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The ASH Annual Meeting & Exposition 2023 will take place from December 9 to December 12, 2023, in San Diego, California, and online. This is the world’s most comprehensive hematology event of the year, featuring the latest research and clinical updates on blood disorders. You can find more information about the meeting program, registration, abstracts, and travel on the official website. Are you interested in attending this meeting?

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ODAC (Oncology Data Advisory Committee for the FDA) --- Next meeting Nov. 16, 2023. The Imetelstat meeting is yet to be scheduled. (EAP is in place and the NDA is pending)

[LWS]

Stifel 2023 Healthcare Conference
Tuesday, November 14th at 9:10 a.m. ET (Fireside Chat)

I am hoping tomorrow that JS will pull everything together and put it into proper prospective. It is time for Imetelstat to be recognized by all (successes to-date and potential going forward). Patients' immediate needs must be fulfilled.

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Previous for reference:

Imetelstat is a miracle blood cancer medicine that uniquely modifies that group of diseases, kills cancer stem cells (in 2 ways), brings about transfusion independence, and will effectively treat (PRs, CRs, possible cures) some cancers in combinations. AML is now in focus as the next step beyond ET, MDS and MF. Imetelstat's safety profile is very good for such a powerful medicine, with few side effects that are reversible and manageable.

With a working EAP in place, the next steps are ODAC review and FDA approval for the NDA.

[LWS]

Here is an outline of the fireside chat (Nov. 14) at the Stifel Healthcare Conference with John Scarlett. I suggest listening to it to get the full, very positive inputs. There is much to expand upon.

1/ Preparing for commercialization at time of approval (very close)
2/ Nature of ODAC changing with opportunity to expose Imetelstat to the world through KOLs and other experts
3/ In middle of ODAC review must be very careful what he says
4/ 20 investors or so at conference
5/ Not clear if a ODAC meeting is necessary; referred to Vertex/CRISPR arrangement ***
6/ Talked about ESAs and luspatercept
7/ Connection between transfusion independence, disease modification, and bone marrow reversals
8/ MOA; unprecedented results
9/ EAP a transition and a community service with an eye on full approval
10/ Will update partnering in 2024
11/ Discussion of Overall Survival Time and the redefinition based upon long survival times with Imetelstat
12/ Salesforce in training
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***Vertex, CRISPR therapy for sickle cell passes FDA panel test
Expert advisers to the agency appeared generally comfortable with the testing Vertex has done to show the safety of the treatment, called exa-cel and now up for U.S. approval.

Published Oct. 31, 2023

[jayfish101]

LWS thanks for the summary of topics discussed today.

[LWS]

Imetelstat is looking more and more like a miracle blood cancer medicine. The MOA is just beginning to be understood with two mechanisms to kill the cancer stem cells, while not harming normal cells. Everyone is waiting for the NDA approval. Then there will be years of research for fine turning the science and treating many cancer types in combinations. Imetelstat is the 'tip of the iceberg'.
+++++++++++++++++++++++++++++++++

From Stifel fireside chat outline:

7/ Connection between transfusion independence, disease modification, and bone marrow reversals
8/ MOA; unprecedented results
++++++++++++++++++++++++++++++++
In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targets to which the drug binds, such as an enzyme or receptor. Receptor sites have specific affinities for drugs based on the chemical structure of the drug, as well as the specific action that occurs there.
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Previous for reference:

Here are five current Imetelstat topics that Geron and potential partners are thinking about:

1/ Ferroptosis
2/ Telomerase & Telomeres
3/ Combinations
4/ Synergies
5/ Oral form potential

[LWS]

Overwhelmingly Positive Data for Oncology ADCOM

The data is there and overwhelmingly positive (trials, conferences, scientific articles, KOLs, MD Anderson and in addition -- Lancet and ASH2023) with more to come. All that is left is for ODAC to be heard from.

JS (John Scarlett) suggested that the ODAC procedure could be used through KOLs to educate many about Imetelstat, both its successes and its potential-- alone and in combinations. The EAP is operational and according to JS can be considered a phase IV with extra and current data available. The transition and timeline from the EAP to the NDA approval should present no problems.

[LWS]

There is only one game now: ODAC (Oncolgy Data Advisory Committee to the FDA) vs. Geron/Imetelstat for NDA (New Drug Application) Status

Most, if not all on this board, believe we know the outcome, with ODAC advising the FDA to approve Imetelstat's NDA. Bp cautions that there is never a sure thing, so in terms of probabilities over 99%, conceding that there may be some last second event on the negative side (not going to happen). We will see after ASH2023, what ODAC has in mind.

[LWS]

Geron Announces Publication in The Lancet of Results from the IMerge Phase 3 Clinical Trial Evaluating Imetelstat in Lower Risk MDS

Business Wire
Mon, Dec 4, 2023, 5:00 AM EST8 min read


Imetelstat is currently under regulatory review by the FDA and EMA for the treatment of transfusion-dependent anemia in adult patients with lower risk MDS

FOSTER CITY, Calif., December 04, 2023--(BUSINESS WIRE)--Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, today announced publication in The Lancet of results from the IMerge Phase 3 trial investigating imetelstat versus placebo in patients with lower risk myelodysplastic syndromes (MDS) relapsed/refractory or ineligible for erythropoiesis stimulating agents (ESAs). The publication is available online and will be available in print at a later date.


"The Lancet’s publication of our IMerge Phase 3 manuscript is a strong validation of the importance of this study within the field, as well as a powerful way of reaching hematologists and other providers globally with these potentially practice-changing results," said Faye Feller, M.D., Executive Vice President, Geron’s Chief Medical Officer. "Based on the highly differentiated qualities of imetelstat reported in this study, we believe that, if approved by regulatory authorities, imetelstat could substantially improve the treatment paradigm in certain patients with lower risk MDS."

Imetelstat is currently under regulatory review by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) for approval in transfusion dependent anemia in patients with lower risk MDS who have failed to respond or have lost response to or are ineligible for ESAs.

"I am pleased with the publication in The Lancet of what I believe are very powerful Phase 3 results with this unique mechanism of action, telomerase inhibition, where we see long-term and durable responses broadly across MDS subgroups. This includes lower risk MDS patients without ring sideroblasts (RS-), ESA-ineligible patients who have high serum EPO levels, and those with high transfusion burden, whose needs are not being met by today’s treatments," said Uwe Platzbecker, M.D., Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, Leipzig University Hospital, Leipzig, Germany, who is the lead author on the manuscript and is an IMerge investigator. "With regards to the safety results, neutropenia and thrombocytopenia were predictable and manageable, with little to no significant clinical consequences. These adverse events commonly occurred in the first three cycles and frequently resolved within two weeks.

[LWS]

Off-label uses

If I understand correctly, the concept of off-label uses offers a great deal of flexibility, once a medicine is NDA approved. A decision can be made between the patient and his doctor. If that is so, Imetelstat, once approved, will be used in many blood cancer situations and in combinations with other approved medicines. The most obvious is the TELOMERE combination (AML---with AbbVie) which has shown outstanding synergies in preclinical testing.
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Previous for review:

bp --- I agree with you that, based upon available data and trials, Imetelstat deserved both a "priority review" and "expanded access" (EAP). I can see why the FDA oncology advisory committee (ADCOM) would want some extra time "standard review" to make sure nothing has been missed, since Imetelstat is a game-changer and the NDA approval will open other doors and off-label clinical use. I suspect that KOL and patient interviews will be overwhelmingly positive. Hopefully, that will lead to a shorter timeline.

[LWS]

ASH2023 (Dec. 9-12) --- Dec. 9 0ral Presentation followed by 3 Poster Presentations

ODAC will have some more very positive information to process Geron's (Imetelstat---"remarkable, compelling, durable, unique, needed now") medicine. The review is taking place now. When will we hear from them? Will there be formal and public hearings? Is the evidence so complete that the formal hearings will be waved (EAP to NDA)?

To state the obvious --- The ball is in ODAC's court. Their decisions about Imetelstat will determine its future. I believe the outcome will be positive for all (patients, investors, Geron insiders), but, as bp says, there are no absolute guarantees.
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Previous:

Imetelstat is currently under regulatory review by the FDA and EMA for the treatment of transfusion-dependent anemia in adult patients with lower risk MDS

"With regards to the safety results, neutropenia and thrombocytopenia were predictable and manageable, with little to no significant clinical consequences. These adverse events commonly occurred in the first three cycles and frequently resolved within two weeks."

[LWS]

JNJ's Interest --- Partner, Collaborator, Investor, Buyout, Deep pockets ????

JNJ had about 10 irons in the fire (2018, I believe, the so-called 'walk') including Imbruvia (approved for JNJ). Imetelstat (IMET), at the time, was promising, but, perhaps, not ready for prime time. JNJ never lost interest as the data got better and better. Now IMET is about to go from EAP to NDA status.

As Kmall has documented, numerous people have moved from JNJ/Jannsen to Geron over the years, including some in leadership. What are JNJ's intentions now? ODAC will speak and NDA will be approved. John Scarlett said (fireside chat) that 2024 is the time to think about partners. Have JNJ and Geron been working together 'under-the-radar'?

[LWS]

Imetelstat is the miracle blood cancer medicine (2 ways to kill cancer stem cells) that is fully manipulated. All are waiting for ODAC & its KOLs to speak.

The ball is in ODAC's (Oncology Data Advisory Committee for the FDA) court now. There is no other game in town.

[biopearl123]

LWS, give it a rest. I will start to limit unnecessarily repetitive posts.

[LWS]

John Scarlett (JS) brought this up (fireside chat)

JS said, that the ODAC may be changing the way it does business, based on the Vertex/CRISPR arrangement and outcome. That is, if the data and outcomes are sufficiently 'remarkable, compelling and durable' (like Imetelstat, for example), formal hearings can be waved with a direct and timely recommendation to the FDA.

He also talked about the unique mechanism of action (MOA) based upon two methods to kill cancer stem cells (1/ Ferroptosis, 2/ Telomerase & Telomeres) that is just beginning to be understood and put into proper perspective.

Perhaps, the most important observation that JS made concerned the connection between transfusion independence, disease modification, and bone marrow reversals --- that is these are not independent occurrences but are closely related to each other on a molecular level.

ODAC has all the data it needs now, with completed trials and new data being constantly supplied by the EAP.
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Ferroptosis is a novel type of programmed cell death dependent on iron. It is characterized by the accumulation of lipid peroxides and is genetically and biochemically distinct from other forms of regulated cell death such as apoptosis. Ferroptosis has been studied in various diseases including cancers, and has boosted a perspective for its usage in cancer therapeutics.

[LWS]

Its all about the Oncology ADCOM now as the waiting continues.

We are all waiting for ODAC (Oncology ADCOM) to indicate how far their review of Imetelstat has currently progressed. Has EAP data been collected and is it part of the data under review? Will there be formal hearings, or is the data so powerful that they will be deemed unnecessary?

We all expect approval of the Imetelstat NDA in a timely and prudent manner, with patient's needs and safety the top considerations. There appears to be no new or important (last minute) medical negatives to further slowdown the NDA approval process. However, with Geron the unexpected is always expected.

[LWS]

Whatever is being done in the short-run to hold down Geron's PPS, the inevitable outcome is that ODAC (with their KOLs) will overwhelmingly and convincingly recommend approvable to the FDA, which they will certainly accept.

NDA approval will follow the functioning EAP, which JS told us can be considered phase 4 data now. The EAP certainly is a very positive indication that Imetelstat's status will be upgraded.

[KTArsenal]

That's a lot of unnecessarily repetitive adverb usage in one paragraph to needlessly make a point subjectively, LWS.

https://youtu.be/dDwXHTcodNg?si=VH2fz4u0xYfhjV0A

[LWS]

ODAC's positive recommendations are critical now.

KTA --- You seem to miss the point completely. The point is, as JS has already told us, that ODAC is now operating in a different mode (Vertex example), where, when the data warrants it (which seems to be the case with Imetelstat's unique trial data and patient's immediate needs), ODAC can forego formal hearings. I believe JS is doing his best to get this critical NDA approval. If you disagree with Imetelstat's medical successes, please state that so that can be properly addressed.

[KTArsenal]

If "JS" has already told us whatever it is that he's telling us, why do you feel the need to repeat what JS has already said?

[LWS]

KTA --- What is your point? Information, properly presented, is a composite of various points of view, including background information, old thoughts and new thoughts. Some people do not have all the information. I am trying to provide some text that I believe is correct, but certainly can be edited.

Anyway, I believe in Imetelstat now (alone) and look forward to off label uses, combinations, synergies, oral Imetelstat, and IMET2.0 (new formulations).