There are many ways to think about partnering

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LWS
Posts: 630
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Thu Jan 05, 2023 4:27 pm

I believe, as investors, we need to divide our thinking into two parts:

Part 1 (Imetelstat as a medicine
) --- Imetelstat appears to be a great medicine without competition (transfusion independence, survival time, safety, kills cancer cells, potential in combinations, etc.). For Geron, with several partners in combinations with their own approved medicines and Imetelstat, the medical future looks very bright. JNJ and AbbVie are the most involved companies with very deep pockets. Imetelstat now has fast-track-status and orphan status.

Part 2 (Geron as a business
) --- Geron is in a very strong negotiating position with Imetelstat, which is in a class by itself. Some question John Scarletts’ business wisdom, timing, and dilution decisions. I suspect he is making good long term decisions, but the short term is often very difficult to understand. John, as long as he is President, will continue to be controversial. The long-term plan is still being formed.

LWS
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Re: There are many ways to think about partnering

Post by LWS » Fri Jan 06, 2023 4:40 pm

This is a follow-up with additional thoughts.

I believe, as investors, we need to divide our thinking into two parts:

Part 1 (Imetelstat as a medicine) --- Imetelstat appears to be a great medicine without competition (transfusion independence, survival time, safety, kills cancer cells, potential in combinations, etc.). For Geron, with several partners in combinations with their own approved medicines and Imetelstat, the medical future looks very bright. JNJ and AbbVie are the most involved companies with very deep pockets. Imetelstat now has fast-track-status and orphan status
.

The news about Imetelstat continues to be very positive, with combinations and oral Imetelstat in the future. We are all waiting for some single-agent approvals from the FDA, EMA, or the UK (MHRA).
Part 2 (Geron as a business) --- Geron is in a very strong negotiating position with Imetelstat, which is in a class by itself. Some question John Scarletts’ business wisdom, timing, and dilution decisions. I suspect he is making good long-term decisions, but the short term is often very difficult to understand. John, as long as he is President, will continue to be controversial. The long-term plan is still being formed
.

These are some random thoughts of mine:


1/ John Scarlett (JS) believes he has a very important blood cancer medicine (with potential in most cancers, including solid tumors) under his control and intends to keep it that way for now and into the foreseeable future.

2/ JS is using tactical partners in combination situations plus MD Anderson as a research and treatment resource.

3/ JS’s objective is to grow Geron into a large company using some deep-pocketed strategic partners (one in the USA and one in Europe) as additional financial resources.

4/ JS plans to maximize the value of Geron stock for all true long-term investors, including himself.

5/ You can’t get to the long-term without surviving the short-term. Some question his short-term tactics.

LWS
Posts: 630
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Sat Jan 07, 2023 4:41 pm

I was optimistic yesterday that we get good news soon on why this offering was necessary now; accelerated approval, partnership, etc. Today's action just doesn't feel right. Like something fishy is going on. You know what they say about the fish.....it rots from the head. -Kmall (Jan 5, 2023 excerpt)
The controversies and surprises around John Scarlett (JS) will continue. We believe we see a 'safe-harbor' close ahead with approvals from the various agencies (FDA, EMA, MHRA/UK). JS is steering the ship and we hope he does not run into the rocks before we get into the harbor. Everything has been questioned about JS at one time or another including his judgement, honesty and self-interest. JS is our captain, in fair weather or foul, and we are along for the ride.

JS knows what he has with Imetelstat (somewhere between a very good blood cancer medicine to a miracle medicine in combinations for many types of cancer). The final chapters have not been written, since the data for combinations is not available yet (TELOMERE for example). Imetelstat has never looked more promising, but, as always, Geron is a business and we have no idea what discussions are in progress.

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 Jan 09, 2023 10:42 pm

Nice detective work Bp. I suspect that Janssen/JNJ still has their hand in the cookie jar, but then again I've been wrong many times before. Either way it certainly appears from the outside looking in big plans are currently underway whatever the circumstance. A little more wait and see won't hurt anyone I guess. -Kmall
The safety, effectiveness, need and additional potential have all been determined for blood cancers as a single-agent and they all look outstanding to me, as we all wait for approvals that seem for certain. The big prizes are in combinations and that is now further down the road as new trials get off of the ground. Both JNJ and AbbVie "have their hands in the cookie jar" with additional ways to kill cancer cells and likely synergies in combinations.

John Scarlett (JS) is in-charge, and he is not sharing everything that he knows. I am here for the long run, which will most likely involve new partners with deep pockets. Imetelstat is an important blood cancer medicine now, with a bright future and JS has "big plans".
Summary--- 3 Ways to Kill Cancer Cells

Venetoclax (approved -- AbbVie), Imbruvia (approved -- JNJ ) and Imetelstat (pending approval -- Geron) all kill cancer cells by different methods. Together, in combinations, there likely will be important synergies.

1/ Imetelstat (telomerase, an enzyme, inhibitor) -- kills cancer cells,
2/ Venetoclax (BCL-2 protein inhibitor) -- kills cancer cells
3/ Imbruvica is a targeted medicine that works by inhibiting the enzyme Bruton tyrosine kinase (BTK), which is part of a crucial signaling pathway in certain cancers, especially B-cell leukemias and lymphomas. By blocking this pathway Imbruvica triggers the death of cancer cells.

LWS
Posts: 630
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Wed Jan 11, 2023 4:32 pm

Geron Announces Experienced Commercial Leadership Hired for Planned Commercial Launch of Imetelstat in the U.S.

01/11/2023


Leadership in place for core commercial functions, including in Market Access, Trade & Channel Relations, Commercial Operations, Analytics, Marketing, Sales and Medical Affairs

Company continues stage-gated commercial readiness efforts for an anticipated commercial launch of imetelstat in lower risk MDS in the first half of 2024 in the U.S. and by the end of 2024 in the EU, assuming regulatory approvals are granted


FOSTER CITY, Calif.--(BUSINESS WIRE)
-- Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, today highlighted multiple additions to its senior commercial leadership team, as it prepares for the potential commercialization in the U.S. market of imetelstat, a first-in-class telomerase inhibitor. Key additions include seasoned professionals with deep operational and launch experience in Trade & Channel Relations, Market Access, Marketing, Medical Affairs and Sales. The Company recently reported positive top-line results from its IMerge Phase 3 clinical trial in lower risk myelodysplastic syndromes (MDS) and is planning a New Drug Application (NDA) submission in the U.S. in mid-2023 and a Marketing Authorization Application (MAA) submission in the EU in the second half of 2023.

Anil Kapur, Geron’s Executive Vice President of Corporate Strategy and Chief Commercial Officer, said, “As we continue to advance development of imetelstat in hematologic malignancies and prepare for potential commercialization, we are gratified by our ability to attract top-level talent to Geron and are excited to have this deeply experienced commercial leadership team in place for our planned commercial launch in lower risk MDS in the U.S. in the first half of 2024, assuming regulatory approval is granted.”


(Information on specific talent)



About Imetelstat

Imetelstat is an investigational, novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from Phase 2 clinical trials provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis stimulating agent, and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment.

About Geron


Geron is a late-stage biopharmaceutical company pursuing therapies with the potential to extend and enrich the lives of patients living with hematologic malignancies. Its investigational first-in-class telomerase inhibitor, imetelstat, harnesses Nobel Prize winning science in a treatment that may alter the underlying course of these diseases. To learn more, visit www.geron.com or follow us on LinkedIn.

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 » Thu Jan 12, 2023 8:01 pm

Focusing on Combinations

We all believe that single-agent approvals are coming, but no one knows exactly when. I am ready to focus on TELOMERE (AbbVie & Geron), a combination of Imetelstat and AbbVie approved medicines for AML. The compelling preclinical data and synergies by combining Imetelstat and Venetoclax appears to be amazing ("nearly 100% apoptotic activity in 96 hours"). I suspect that there has been experimental activity (under the radar) that we do not know about yet, and that both companies are very confident about clinical successes from the new trials.
-----------------------------------------------------------------------
Review from Previous Posts:

TELOMERE is a Phase 1/2 clinical trial evaluating 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 a safe dose of each of the combinations. The primary objective of the Phase 2 portion of the study is overall response rate for each of the combination regimens. The study is expected to be open for patient enrollment in the second half of 2022.


***Results (preclinical): 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. ***

This combination treatment and potential cure is made more likely by the recent AML evidence that Imetelstat kills cancer-stem-cells.

I have high hopes that Imetelstat will be approved in the near future for single-agent use based upon its trial data, safety profile, orphan status and fast track. I am focused on the preclinical work combining Imetelstat and Venetoclax that achieved "nearly 100%" apoptotic activity in 96 hours. This combination, if successful at the clinical level, is breakthrough territory establishing the importance of Imetelstat cancer combinations. I suspect that AbbVie and Geron have done substantial additional testing in the last few years and are very confident about the outcome. This is likely to be an enduring relationship.

LWS
Posts: 630
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Fri Jan 20, 2023 4:52 pm

Summary and Quest for Updates and Additional Information

Imetelstat is already a proven and exceptional single-agent blood cancer medicine. We are in the process of discovering how far the combination synergies go in creating “miracle cancer medicines” and perhaps “miracle cures” for a variety of cancers with other approved medicines (from AbbVie & JNJ for example).

The proof positive will be approvals (from FDA, EMA, MHRA in UK). We believe that they are coming, but no one knows when, considering that fast track and priority reviews are in the mix. The pieces of this puzzle seem to be coming together.
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
For Review

The topic and discussion of this thread centered on JNJ-74856665 used in combination with Azacitidine or Venetoclax. Similar to the upcoming TELOMERE P1/2 Clinical Trial using Imetelstat in combination with Azacitidine or Venetoclax. Once approved, Imetelstat as a single agent off label could possibly be a more efficient and effective means of treatment. However, for certain cancers and in the case of the patient in this discussion with AML and a two month survival expectancy, certain drug combinations, or in this example, the combination of JNJ-74856665 with Azacitidine or Venetoclax, has so far proven successful as a "miracle cure" - cited in the article. -Kmall
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
For Review

Summary--- 3 Ways to Kill Cancer Cells

Venetoclax (approved -- AbbVie), Imbruvia (approved -- JNJ ) and Imetelstat (pending approval -- Geron) all kill cancer cells by different methods. Together, in combinations, there likely will be important synergies.

1/ Imetelstat (telomerase, an enzyme, inhibitor) -- kills cancer cells,
2/ Venetoclax (BCL-2 protein inhibitor) -- kills cancer cells
3/ Imbruvica is a targeted medicine that works by inhibiting the enzyme Bruton tyrosine kinase (BTK), which is part of a crucial signaling pathway in certain cancers, especially B-cell leukemias and lymphomas. By blocking this pathway Imbruvica triggers the death of cancer cells

LWS
Posts: 630
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Fri Jan 27, 2023 5:33 pm

JNJ Mysteries and JNJ-74856665 now in Focus

Combinations are in focus with JNJ still very much in the picture in ways that we do not understand. As Kmall continues to report, JNJ/Jannsen people keep finding their way to Geron. We assume, because of their special knowledge, the future for Geron and Imetelstat looks very bright to them. We do not know what discussions are taking place now about alliances, partnerships and perhaps buyouts. We also do not know the impact of fast-track and priority reviews for accelerating approvals (from FDA, EMA, MHRA (UK)). Venetoclax, Imbruvica and Imetelstat are likely key ingredients in both combinations (in unknown amounts), and all individually kill cancer cells (synergies).

What else is in these mixes?


---------------------------------------------------------------------
For Review
The topic and discussion of this thread centered on JNJ-74856665 ("miracle cure") used in combination with Azacitidine or Venetoclax. Similar to the upcoming TELOMERE P1/2 Clinical Trial using Imetelstat in combination with Azacitidine or Venetoclax. -- from Kmall


JNJ Importance to Imetelstat (Past, Present, Future)


More than any other company JNJ has had a continuing interest in Imetelstat, from the time of their close association with Geron leading to the “walk” (2018, I believe) where JNJ said that Imetelstat would eventually get approved, to current staff with backgrounds at JNJ/Janssen and ASH 2022, to “miracle cures” such as JNJ – 74856665 and development of oral Imetelstat.

All of this is suitable for discussion, as we wait for ASH and the January data release. There are many moving parts and we still do not know how they all fit together.
-----------------------------------
Anyone remember the confidential SEC filings of a few years ago? I wondered why Geron would value potential income as of 2030 in both MF and MDS. My guess is that when Jansen realized the FDA would require a PIII MF study (recall that MDS was actually not part of the Janssen agreement until later) they turned Geron loose but perhaps not before the wiley Dr. Scarlett might have forged a secret agreement for them to take another look based on valuations of income as of a certain date once further data was available. So are the 2030 date and the confidential agreement related? Just putting it out there for speculation. I do think future MF study results are supported by what we already know about mutational analysis in the the PIII MDS study. I don’t want to be the guy to start with conspiracy theories but we all sort of think the ties with J and J are not completely severed and might still exist. Sure would like to know what is in that confidential SEC filing… from biopearl

LWS
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Re: There are many ways to think about partnering

Post by LWS » Sat Feb 04, 2023 4:58 pm

We don’t know what we don’t know, so we can only take ‘educated guesses'. I believe (hope) that Geron is waiting for single-agent approvals (MDS & MF) before anyone gets too far involved in oral Imetelstat, combinations and synergies. At this point in time, the single-agent safety and effectiveness of Imetelstat is well documented, but for the investment world to get excited, we need those first approvals (FDA, EMA, MHRA/UK). Without those approvals (which also opens up off-label uses) we are spinning our wheels.

-------------------------------
For Review
Even more worrisome perhaps is a now two month delay of the hyped IMpress AML Clinical Trial, which in turn subsequently delays the TELOMERE Clinical Trial with no explanation as to why from the company. Sure feels like we're back to the same old same old to me. -Kmall
---------------------------------------------------------------------------
We are all working under the assumption that there is no misinformation about Imetelstat in the trials, including (primarily) safety and effectiveness. I believe that single-agent approvals are close, with fast-track and orphan status in place, and priority reviews possible. Then we can talk more about off-label possibilities and combination synergies. –LWS
----------------------------------------------------------------------------
Summary--- 3 Ways to Kill Cancer Cells

Venetoclax (approved -- AbbVie), Imbruvia (approved -- JNJ ) and Imetelstat (pending approval -- Geron) all kill cancer cells by different methods. Together, in combinations, there likely will be important synergies.

1/ Imetelstat (telomerase, an enzyme, inhibitor) -- kills cancer cells,
2/ Venetoclax (BCL-2 protein inhibitor) -- kills cancer cells
3/ Imbruvica is a targeted medicine that works by inhibiting the enzyme Bruton tyrosine kinase (BTK), which is part of a crucial signaling pathway in certain cancers, especially B-cell leukemias and lymphomas. By blocking this pathway Imbruvica triggers the death of cancer cells

biopearl123
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Re: There are many ways to think about partnering

Post by biopearl123 » Sun Feb 05, 2023 12:26 am

If it were true that Geron is waiting for approval (so are we), then they shouldn’t be guiding start dates for studies that they can’t deliver.

LWS
Posts: 630
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Sun Feb 05, 2023 4:17 pm

Imetelstat has Zero Approvals

The most obvious issue is that Imetelstat has never been approved for anything (except orphan status) by any important agency (USA, Europe, UK, other). Much of the focus recently has been on AML and combinations. Perhaps, there has been some discussion about the risks, expenses and liabilities about experimenting with an unapproved drug, especially when everything (trials, data, medical results) is available and in place to get single-agent approvals.

It seems reasonable and logical to me that Geron, AbbVie and JNJ have decided to put all their effort behind getting meaningful approvals for Imetelstat (which are absolutely needed) and slowing down a bit on the AML studies and combination synergies. Also, consider the possibilities of off-label uses.
------------------------------------
For Review
Venetoclax (approved -- AbbVie), Imbruvia (approved -- JNJ ) and Imetelstat (pending approval -- Geron) all kill cancer cells by different methods. Together, in combinations, there likely will be important synergies --- from LWS

If it were true that Geron is waiting for approval (so are we), then they shouldn’t be guiding start dates for studies that they can’t deliver.—from BP

The topic and discussion of this thread centered on JNJ-74856665 ("miracle cure") used in combination with Azacitidine or Venetoclax. Similar to the upcoming TELOMERE P1/2 Clinical Trial using Imetelstat in combination with Azacitidine or Venetoclax. -- from Kmall
Even more worrisome perhaps is a now two month delay of the hyped IMpress AML Clinical Trial, which in turn subsequently delays the TELOMERE Clinical Trial with no explanation as to why from the company. Sure feels like we're back to the same old same old to me. -Kmall

LWS
Posts: 630
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Mon Feb 06, 2023 4:02 pm

The Power of Off-Label Use?

Once Imetelstat gets approved for one of its many single-agent properties in several blood cancers (especially MDS & MF with ET in the background), how widely can it be used? More than one approved medicine can be taken for the same condition. For example, I now take two medicines for my blood pressure, and at one time I took three together.

I know little about off-label possibilities. Venetoclax is an approved medicine, and Imetelstat is not (both components in the TELOMERE AML trial, yet to get off of the ground). What are the possibilities of using two approved blood cancer medicines without extensive further trials? That may be part of Geron's and AbbVie's thinking about TELOMERE. The preclinical results (with synergies) were spectacular.

The focus needs to be on getting Imetelstat approved for something, somewhere ASAP.


Note: We don't know much about JNJ-74856665 ("miracle cure"--Kmall). We believe it has been used successfully in England for AML, and is a combination with Venetoclax, likely Imbruvia, and with thoughts about Imetelstat (including oral form).
-------------------------------------------------
Venetoclax (approved -- AbbVie), Imbruvia (approved -- JNJ ) and Imetelstat (pending approval -- Geron) all kill cancer cells by different methods. Together, in combinations, there likely will be important synergies --- from LWS

LWS
Posts: 630
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Sat Feb 11, 2023 5:59 pm

Off-Label Drug Use in Cancer Treatment ---NIH (National Cancer Institute)

What are off-label drugs?


Drugs can be legally sold in the United States only after the Food and Drug Administration (also known as the FDA) has approved them. Drugs are approved after research shows they are safe and effective for a specific use.

Off-label drug use refers to the practice of prescribing a drug for a different purpose than what the FDA approved. This practice is called “off-label” because the drug is being used in a way not described on its package insert. This insert is known as its “label.”


The label describes details about the drug, such as

what the drug is made of
how it works in the body
the research studies that led to its approval
side effects it may cause

The FDA must make sure that a drug is safe and effective for a specific use. However, it does not control the decision doctors make about which drugs to use for their patients. This means that once the FDA approves a drug, doctors can prescribe it for any purpose they think makes sense for the patient.


Off-label uses may include using an approved drug for a different type of cancer than the one it is approved to treat
at a different dose or frequency to treat a child when it is approved to treat adults

Off-label uses of a drug can become approved uses if the company that makes it obtains approval from the FDA. To gain the added approvals, the company must conduct research studies to show that the treatment is safe and effective for the new uses. However, a company may decide not to invest time and money in this research.

The role of off-label drug use in cancer treatmen
t

Research has shown that off-label use of drugs is very common in cancer treatment. Often, usual care for a specific type or stage of cancer includes the off-label use of one or more drugs.

Off-label drug use is common in cancer treatment because many cancer drugs are effective against more than one type of cancer.

Cancer treatment often involves the use of combination chemotherapy.

Combination chemotherapy (which is treatment using more than one drug) is effective in treating many types of cancer. Examples of combination chemotherapy include:


R-CVP to treat non-Hodgkin lymphoma
CMF and TAC to treat breast cancer
BEACOPP to treat Hodgkin lymphoma
FOLFOX to treat colon cancer
These combinations might include one or more drugs not approved for the type of cancer they are being used to treat.

The FDA usually does not approve combinations of chemotherapy. There are so many of them that it would not be practical to approve each combination.

Research studies find new uses for drugs that are already approved. The results of research studies are published in medical journals and shared in the medical community. Doctors then adopt the new use and it may become an accepted and widely-used treatment for a different cancer, even if the FDA has not approved the drug for that use.



Drawbacks to off-label drug use


There are times when off-label drug use may cause harm, such as when it has not been shown to be effective against a certain cancer there is no reason to believe the drug might be effectivethe possible risks of giving the drug outweigh the possible benefits

However, if your doctor prescribes a drug for an off-label use to treat your cancer, they are basing the decision on knowledge of and experience with the drug, as well as on research that shows it might be helpful for your stage and type of cancer.


Health insurance coverage of off-label drugs in cancer treatment
Medicare and many insurance companies pay for off-label drugs for cancer treatment, as long as the off-label uses are listed in an approved compendium. A compendium is a collection of drug summaries put together by experts who have reviewed data about the drug’s use in patients.

If your doctor prescribes an off-label drug for your treatment, check your plan to make sure the drug is covered. If coverage is denied, it may be helpful for the doctor to provide the insurance company with copies of documents that support the suggested off-label use.

Questions to ask your doctor about off-label drugs

Discussing these questions with your doctor can help you understand why your doctor might prescribe an off-label drug for you.

Why do you think the off-label use of this drug will help the type of cancer that I have?

Is the off-label drug likely to work better than an approved drug?

What are the risks and benefits of treatment with this drug?

Will my health insurance cover my treatment with this drug?

If my treatment involves combination chemotherapy and one of the drugs is off-label, will my health insurance cover it?

Reviewed: January 13, 2022
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
It seems reasonable and logical to me that Geron, AbbVie and JNJ have decided to put all their effort behind getting meaningful approvals for Imetelstat (which are absolutely needed) and slowing down a bit on the AML studies and combination synergies. Also, consider the possibilities of off-label uses

LWS
Posts: 630
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Thu Feb 23, 2023 4:37 pm

This is a review. Geron and Imetelstat are at an important juncture with NDAs, fast-track approvals and off-label uses all in focus.

Imetelstat can go in many directions from single-agent to a variety of combinations, with numerous patents now in place. Disease modification, the good safety profile, and the ability to kill cancer-stem-cells (normal cells not affected), all are unique and very positive factors. Single-agent approvals are close, with the UK (MHRA) likely first. The FDA approval in the USA will be the most important.

1. Big pharma---Bayer AG/Vividion, AbbVie, JNJ/Janssen
2. People-- Dr. Rizo, Dr. Feller, Dr. Scarlett
3. Imetelstat---single-agent, blood cancers, combinations, vaccines, solid tumors, telomeres & telomerase interactions
4. Approvals needed--- UK, EU, USA
5. Processes-- staff, manufacturing
6. Collaborator--- MD Anderson

Potential partners and collaborators

The interest in Imetelstat is now universal. These seem to be the companies or groups that Geron is most actively involved with to get approvals and to advance Imetelstat’s medical uses. The timeline for some single-agent approval is still unknown. Combination trials are underway.

1/ USA companies: JNJ, AbbVie, Incyte

2/ European companies: Bayer AG, Novo Nordisk, Novartis

3/ Groups: MD Anderson, NIH (Cancer Moonshot)

Geron and staff will continue to surprise us based upon past experiences.
```````````````````````````````````````````````````````
Combinations studies in progress, with more to come:

(With Incyte)-- IMproveMF Phase 1 study of imetelstat + ruxolitinib in frontline MF in May 2022

(With AbbVie) -- TELOMERE Phase 1/2 study of imetelstat + HMAs or venetoclax in R/R
AML in 2H 2022

LWS
Posts: 630
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Thu Mar 09, 2023 4:02 pm

JNJ never left. They have always supported Imetelstat and Geron. Their #1 interest has been Imbruvia, but their continuing interest in Imetelstat has never lessened. Now they are making up for lost time, with the NDA acceptance and approvals in focus.

Here is a summary of some previous material for future discussion:


~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
JNJ Importance to Imetelstat (Past, Present, Future)

More than any other company JNJ has had a continuing interest in Imetelstat, from the time of their close association with Geron leading to the “walk” (2018, I believe) where JNJ said that Imetelstat would eventually get approved, to current staff with backgrounds at JNJ/Janssen and ASH 2022, to “miracle cures” such as JNJ – 74856665 and development of oral Imetelstat.

All of this is not clearly in focus, and is suitable for discussion, as we wait for ASH and the January data release. There are many moving parts and we still do not know how they all fit together.

1/ TALC – a JNJ problem that is still not resolved. JNJ is splitting into two companies.
2/ Money – As originally constructed (before walk), not a good deal for JNJ
3/ Better Bets (Imbruvica) – A JNJ fully owned drug, that is suitable for combinations
4/ Janssen and JNJ support – staff and Korean manufacturing facility
5/ JNJ deep pockets
6/ JS statement – “Bigger than all of us”
7/ Oral form of Imetelstat --- In JNJ new formulations, perhaps
8/ “miracle cure"

The focus needs to be on getting Imetelstat approved for something, somewhere ASAP.

Note: We don't know much about JNJ-74856665 ("miracle cure"--Kmall). We believe it has been used successfully in England for AML, and is a combination with Venetoclax, likely Imbruvia, and with thoughts about Imetelstat (including oral form).
-------------------------------------------------
Venetoclax (approved -- AbbVie), Imbruvia (approved -- JNJ ) and Imetelstat (pending approval -- Geron) all kill cancer cells by different methods. Together, in combinations, there likely will be important synergies --- from LWS
---------------------------------------------------------------------------
We are all working under the assumption that there is no misinformation about Imetelstat in the trials, including (primarily) safety and effectiveness. I believe that single-agent approvals are close, with fast-track and orphan status in place, and priority reviews possible. Then we can talk more about off-label possibilities and combination synergies. –LWS
----------------------------------------------------------------------------
Summary--- 3 Ways to Kill Cancer Cells

Venetoclax (approved -- AbbVie), Imbruvia (approved -- JNJ ) and Imetelstat (pending approval -- Geron) all kill cancer cells by different methods. Together, in combinations, there likely will be important synergies.

1/ Imetelstat (telomerase, an enzyme, inhibitor) -- kills cancer cells,
2/ Venetoclax (BCL-2 protein inhibitor) -- kills cancer cells
3/ Imbruvica is a targeted medicine that works by inhibiting the enzyme Bruton tyrosine kinase (BTK), which is part of a crucial signaling pathway in certain cancers, especially B-cell leukemias and lymphomas. By blocking this pathway Imbruvica triggers the death of cancer cells
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Preclinical History for Review

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
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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. ****

There has to be considerable interest, from all, in the fact that Imetelstat can kill cancer stem cells, while leaving normal cells alone. The research opportunities in Cancer Moonshot projects are unmatched.
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HOW DO B-CELL LYMPHOMA INHIBITORS WORK?

B-cell lymphoma inhibitors are a class of drugs used to treat certain types of cancers such as chronic lymphocytic leukemia (a type of cancer that begins in the white blood cells), small lymphocytic lymphoma (a type of cancer that begins in the lymph nodes), and acute myeloid leukemia (cancer of the blood and bone marrow) in people 75 years of age or older or adults who have medical conditions that prevent them from being treated with other chemotherapy medications.

The only drug that belongs to this class is “venetoclax” which works by inhibiting the anti-apoptotic protein B-cell lymphoma-2 (BCL-2; necessary regulator of anti-cell programmed death process).
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Combinations are in focus with JNJ still very much in the picture in ways that we do not understand. As Kmall continues to report, JNJ/Jannsen people keep finding their way to Geron. We assume, because of their special knowledge, the future for Geron and Imetelstat looks very bright to them. We do not know what discussions are taking place now about alliances, partnerships and perhaps buyouts. We also do not know the impact of fast-track and priority reviews for accelerating approvals (from FDA, EMA, MHRA (UK)). Venetoclax, Imbruvica and Imetelstat are likely key ingredients in both combinations (in unknown amounts), and all individually kill cancer cells (synergies).

What else is in these mixes?
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Anyone remember the confidential SEC filings of a few years ago? I wondered why Geron would value potential income as of 2030 in both MF and MDS. My guess is that when Jansen realized the FDA would require a PIII MF study (recall that MDS was actually not part of the Janssen agreement until later) they turned Geron loose but perhaps not before the wiley Dr. Scarlett might have forged a secret agreement for them to take another look based on valuations of income as of a certain date once further data was available. So are the 2030 date and the confidential agreement related? Just putting it out there for speculation. I do think future MF study results are supported by what we already know about mutational analysis in the the PIII MDS study. I don’t want to be the guy to start with conspiracy theories but we all sort of think the ties with J and J are not completely severed and might still exist. Sure would like to know what is in that confidential SEC filing… from biopearl
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LWS
Posts: 630
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Fri Mar 17, 2023 3:32 pm

All the 'moving-parts' leading up to the complete acceptance of the modular NDA appear to be moving in the right direction.

There is almost $450 million in cash on hand, with SVB bank crisis being a non-event for Geron. Geron (Imetelstat) has many irons in the fire, but none can come to fruition until the FDA and/or the EMA accept, in full, the NDA and follow-up with fast-track approvals. The acceptances and approvals, considering everything, have a very high probability of a satisfactory outcome (I would never say, "a sure thing").

Here are the items that we are all thinking about.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Potential partners and collaborators

The interest in Imetelstat is now universal. These seem to be the companies or groups that Geron is most actively involved with to get approvals and to advance Imetelstat’s medical uses. The timeline for some single-agent approval is still unknown. Combination trials are underway.

1/ USA companies: JNJ, AbbVie, Incyte

2/ European companies: Bayer AG, Novo Nordisk, Novartis

3/ Groups: MD Anderson, NIH (Cancer Moonshot)

Geron and staff will continue to surprise us based upon past experiences.

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Summary--- 3 Ways to Kill Cancer Cells

Venetoclax (approved -- AbbVie), Imbruvia (approved -- JNJ ) and Imetelstat (pending approval -- Geron) all kill cancer cells by different methods. Together, in combinations, there likely will be important synergies.

1/ Imetelstat (telomerase, an enzyme, inhibitor) -- kills cancer cells,
2/ Venetoclax (BCL-2 protein inhibitor) -- kills cancer cells
3/ Imbruvica is a targeted medicine that works by inhibiting the enzyme Bruton tyrosine kinase (BTK), which is part of a crucial signaling pathway in certain cancers, especially B-cell leukemias and lymphomas. By blocking this pathway Imbruvica triggers the death of cancer cells
--------------------------------------------------------------------------------

JNJ Importance to Imetelstat (Past, Present, Future)


More than any other company JNJ has had a continuing interest in Imetelstat, from the time of their close association with Geron leading to the “walk” (2018, I believe) where JNJ said that Imetelstat would eventually get approved, to current staff with backgrounds at JNJ/Janssen and ASH 2022, to “miracle cures” such as JNJ – 74856665 and development of oral Imetelstat.
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Dr. Sergei Gryaznov (at MAIA), formerly Geron's (NASDAQ: GERN) Chief Scientist in Nucleic Acid Chemistry, is the named inventor of GRN163L, also known as Imetelstat. He said that Geron should go back to developing Imetelstat for ET/PV.

LWS
Posts: 630
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Sun Apr 02, 2023 4:35 pm

The NDA is now 'the whole ball of wax'. With it Geron and telomere/telomerase considerations go to the 'front of the pack'. Without it, Imetelstat becomes that promising medicine that did not quite make it, and Geron collapses. Everything points to acceptances and approvals by the various agencies, with the FDA being the most important, but 'nothing is a sure thing' (the investment speculation & FUDD).

We can do nothing at this point in time but wait. We all hope that John Scarlett knows what he is doing to meet patients' needs, and, at the same time, considers the long-term investor's interest. Goldman Sachs' recent interest seems to be a step in that direction. I am very hopeful, but always cautious
.

======================================================================================================
Material for Reference
The interest in Imetelstat is now universal. These seem to be the companies or groups that Geron is most actively involved with to get approvals and to advance Imetelstat’s medical uses. The timeline for some single-agent approval is still unknown. Combination trials are underway.

1/ USA companies: JNJ, AbbVie, Incyte

2/ European companies: Bayer AG, Novo Nordisk, Novartis

3/ Groups: MD Anderson, NIH (Cancer Moonshot)

Geron and staff will continue to surprise us based upon past experiences.
```````````````````````````````````````````````````````

Combinations studies in progress, with more to come:

(With Incyte)-- IMproveMF Phase 1 study of imetelstat + ruxolitinib in frontline MF in May 2022

(With AbbVie) -- TELOMERE Phase 1/2 study of imetelstat + HMAs or venetoclax in R/R
AML in 2H 2022
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Note: We don't know much about JNJ-74856665 ("miracle cure"--Kmall). We believe it has been used successfully in England for AML, and is a combination with Venetoclax, likely Imbruvia, and with thoughts about Imetelstat (including oral form).
-------------------------------------------------
Venetoclax (approved -- AbbVie), Imbruvia (approved -- JNJ ) and Imetelstat (pending approval -- Geron) all kill cancer cells by different methods. Together, in combinations, there likely will be important synergies --- from LWS

LWS
Posts: 630
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Wed Apr 05, 2023 4:36 pm

Many believe that JNJ TALC problems have always been connected to both the JNJ 'walk' and JNJ's continuing interest in Imetelstat, as a critical part of treating blood cancers and beyond in combinations. Certainly, the TALC problem has been a major headache for JNJ. The science may be on their side, but the juries have not been their friends. It appears that this is close to a settlement.

JNJ will always be connected to Imetelstat in some manner (partner, collaborator, buyout, deep pocket supporter ?).
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For Reference & Review:
J&J's Talc Litigation Proposal Is Positive For Stock And Removes Key Overhang, Say JPM Analysts -- MarketWatch
April 05, 2023
Dow Jones Newswires


Johnson & Johnson's (JNJ) decision to pay up to $8.9 billion over 25 years to settle claims connected with cosmetic- talc litigation is a positive for the stock as it removes the overhang of negative headlines, JP Morgan analysts said Wednesday. "A settlement could significantly accelerate the timeline for talc litigation resolution relative to ongoing litigation (with investors broadly avoiding litigation/uncertainty in the sector) and the $8.9 billion committed is in- line with our $8-10 billion estimate (which translates to $3.50/share for JNJ),' analysts wrote in a note to clients. " And while there is still uncertainty on if this bankruptcy re-filing will be accepted by all parties involved, we do note that JNJ has secured commitments from over 60,000 current claimants to support a global resolution on these terms." A federal appeals court in January rejected the consumer products and drug maker's move to place its talc liabilities into bankruptcy, saying that the subsidiary was not in financial distress. Johnson & Johnson has faced thousands of lawsuits alleging that cosmetic talc in its products was connected to cancers, asbestos poisoning and other illnesses. The stock rose 2.9% premarket but has fallen 10% in the last 12 months, while the S&P 500 has fallen 9%.
-Ciara Linnane
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

JNJ Importance to Imetelstat (Past, Present, Future)


More than any other company JNJ has had a continuing interest in Imetelstat, from the time of their close association with Geron leading to the “walk” (2018, I believe) where JNJ said that Imetelstat would eventually get approved, to current staff with backgrounds at JNJ/Janssen and ASH 2022, to “miracle cures” such as JNJ – 74856665 and development of oral Imetelstat.

All of this is not clearly in focus, and is suitable for discussion, as we wait for ASH and the January data release. There are many moving parts and we still do not know how they all fit together.

1/ TALC – a JNJ problem that is still not resolved. JNJ is splitting into two companies.
2/ Money – As originally constructed (before walk), not a good deal for JNJ
3/ Better Bets (Imbruvica) – A JNJ fully owned drug, that is suitable for combinations
4/ Janssen and JNJ support – staff and Korean manufacturing facility
5/ JNJ deep pockets
6/ JS statement – “Bigger than all of us”
7/ Oral form of Imetelstat --- In JNJ new formulations, perhaps
8/ “miracle cure”

LWS
Posts: 630
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Sun Apr 09, 2023 8:47 pm

Some Thoughts:

1/ A medically independent FDA is desirable and necessary.
2/ The FDA needs to remain non-political and objective.
3/ Patients’ needs have to come first.
4/ The modular NDA for Imetelstat needs to be reviewed, accepted and approved by the FDA and others.
5/ Geron has a business side and a medical side that do not always seem to be on the same page.
6/ JNJ has been part of Imetelstat’s past, present and most likely its future (along with AbbVie).

LWS
Posts: 630
Joined: Thu Jul 14, 2016 2:00 am

Re: There are many ways to think about partnering

Post by LWS » Thu Apr 13, 2023 9:17 pm

My candidate for an ex-USA partner is Nova Nordisk. With diabetes as a staple and weight loss as a new source of profit, Imetelstat and all of its cancer potential would seem to make sense. The other European companies that have a relationship with Geron are Bayer AG and Novartis.

Here is an example of an off-label use that paid off big-time. Once Imetelstat gets approved, all sorts of off-label possibilities and explorations will open up. An NDA approval is critical now for patients and investors.

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Weight-Loss Drug Demand Lifts Novo Nordisk -- Market Talk
April 13, 2023


Novo Nordisk pre-announced its 1Q sales surged 25% on rising demand for its anti-obesity drug Wegovy and cousin drug Ozempic, which is approved for diabetes but widely used for weight loss. The Danish drugmaker boosted its outlook for full-year sales growth to up to 30%, versus a prior forecast of up to 19%, at constant-exchange rates. The company has added a second contract manufacturer to boost output of Wegovy, which faced supply constraints for much of 2022. Full quarterly results are due out May 4. Novo shares are up about 1.6%. (peter.loftus@wsj.com; @Loftus)


(END) Dow Jones Newswires
April 13, 202309:02 ET (13:02 GMT)
Copyright (c) 2023 Dow Jones & Company, Inc.

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