P1/2 TELOMERE Clinical Trial delayed......

[kmall]

YMB poster RJM - has pointed out that on Pg. 4 of the September 2022 Geron Corporation Presentation slides, that the P1/2 TELOMERE Clinical Trial has been delayed "pending IMpress data."

I've reached out to Aron Feingold concerning this issue and I hope to be hearing back from her, hopefully sooner rather than later.

Until then, any thoughts on why this change was made and why no PR for an update on this change?

The company website still has TELOMERE initiating in the second half of 2022.....

investor@geron.com
October 20, 2022 8:37am


Hi Aron,

I recently noticed that on Page 4 of Geron's September Corporate presentation that the P1/2 TELOMERE Clinical Trial has been "delayed" - "pending IMpress data"...

https://s24.q4cdn.com/668523011/files/d ... -FINAL.pdf

....even though the Geron website still has TELOMERE initiating in the second half of 2022: "The study is expected to be open for patient enrollment in the second half of 2022."

https://www.geron.com/patients/clinical-trials/

Can you possibly elaborate as to why this change was made?

Thank you in advance,

Kmall
Geron Investor

[biopearl123]

Kmall, yes JS mentioned it recently in one of his presentations and I called it to the boards attention either here or on YMB. The reason given—- wait for it—-yup THE FDA!! They apparently wanted single agent data first.

[kmall]

Thanks for the input Bp. I wasn't privy to listening to any of the last 3 or 4 CC's. I find it unfathomable that the FDA wouldn't want to move forward with a P1/2 Clinical Trial for AML patients when their opinions are so limited as is. Makes zero sense from a patient or clinical standpoint, especially given TI data from P2 IMerge and P2 IMbark OS rates. It certainly feels like the FDA has done more roadblocking than clearing on this approval pathway......to me anyway. -Kmall

[biopearl123]

World class, non company investigators thought it was safe enough. There is strong non clinical work to support it. There is internal company data to support it. And yet… One wonders, does the FDA actually ask the leaders in the field for their opinion before throwing up the usual roadblocks? Did they see any red flags in the protocol? The FDA is entrusted to make good decisions on behalf of patients. Have they done that with regard to Imetelstat? One wonders…

[biopearl123]

Kmall, for IMpress: 46 patients who have failed everything. Time from onset of treatment to assessment of primary end point 4 months. Since this study is unblinded, it is hard to know at what point the FDA would assess to allow TELOMERE to go or not go. Perhaps after the first 10 patients? Just a guess. bp

[kmall]

Bp: it looks like they're planning a start date in December for IMpress:

"Estimated Study Start Date:
December 2022"

https://clinicaltrials.gov/ct2/show/NCT ... w=2&rank=1

If you're assessment of 4 months and 10 patients is correct, then "perhaps" the FDA reviews data late spring/early summer? Better than never I suppose, but from my estimate the TELOMERE CT could be pushed back an additional 9 months to a year, best case scenario?

Still a travesty in my book, considering what these patients face and the opportunity Imetelstat potentially holds for them. -Kmall

[biopearl123]

Agree it probably amounts to a years delay.

[kmall]

Bp: Forgive me for beating a dead horse here....

But if I'm an MDS patient, I have a roughly 33% chance of my disease progressing to AML. Although technically, AML is a separate indication, it evolves from MDS.

P2 IMerge (MDS) had a proven median TI duration of up to 86% in High Transfusion–Burden Patients With Lower-Risk MDS......

https://ascopubs.org/doi/abs/10.1200/JCO.20.01895

"RESULTS:
Data from the phase II part of the study are reported. Of 57 patients enrolled and treated (overall population), 38 were non-del(5q) and hypomethylating agent and lenalidomide naïve (subset population). The 8- and 24-week RBC TI rates in the overall population were 37% and 23%, respectively, with a median TI duration of 65 weeks. In the subset population, 8- and 24-week RBC TI rates were 42% and 29%, respectively, with a median TI duration of 86 weeks. Eight-week TI rate was observed across all subgroups evaluated. Cytogenetic and mutational data revealed a reduction of the malignant clones, suggesting disease modification activity. The most common adverse events were cytopenias, typically reversible within 4 weeks.

CONCLUSION:
Imetelstat treatment results in a meaningful, durable TI rate across a broad range of heavily transfused patients with LR MDS who are ineligible for or relapsed/refractory to ESAs. Biomarker analyses indicated effects on the mutant malignant clone.

© 2020 by American Society of Clinical Oncology"*

*Note the publisher of this article - American Society of Clinical Oncology

The American Society of Clinical Oncology has a membership base of 45,000. This is a highly regarded Clinical Organization who published this finding in 2020. It's now October 2022...going on 3yrs since this abstract was published. The current P3 IMerge CT is also winding down with a "Primary Completion Date: January 15, 2023"

https://clinicaltrials.gov/ct2/show/NCT ... =2&rank=10

Surely if there were any safety concerns, the DMSB would have chimed in by now.

Also of note in the above abstract from the ASCO:
"Cytogenetic and mutational data revealed a reduction of the malignant clones, suggesting disease modification activity."

I'm not understanding a delay here for the TELOMERE CT in AML patients. Do we know the reasoning from the FDA other than proving as a single agent first?

Thanks again for your insight here. -Kmall

[biopearl123]

The only thing I can think of might be an uncontrolled tumor lysis syndrome in response to treatment. Oncologists are skilled at treating such. Otherwise it is a head scratcher but seems to be in keeping with the multiple roadblocks set up by the agency from the time Dr. Tefferi’s second study was scratched. Recall one objection the agency had was liver effects despite endorsement from a panel of hepatologists as well as a failure to reach Hy’s law. Many objections, and we agree on this, seem to me at best overly cautious and and worse contrived.

[kmall]

My response from Aron Feingold:

Hi Kmall,

Thank you for the inquiry. The update in the September corporate deck is correct and we’re working on updating the website appropriately.

The investigators leading the TELOMERE study decided to defer the start of the study. They believe that single agent imetelstat data from IMpress would help inform the dose and schedule to be used in the two combination dosing regiments to be evaluated in TELOMERE.


Hope that helps.


Kind regards,

Aron
Vice President, Investor Relations & Corporate Communications
Geron Corporation • 919 E. Hillsdale Boulevard, Suite 250, Foster City, CA 94404


**Geron has recently updated it's website to reflect the above mentioned.....

"The planned start date for TELOMERE is pending IMpress single-agent imetelstat data. We expect such data to help inform the dose and schedule to be used in the two combination dosing regimens to be evaluated in TELOMERE."

https://www.geron.com/patients/clinical-trials/

[biopearl123]

Kmall, thanks for sharing Aron’s letter. I believe, more exactly that Dr. Scarlett said the TELOMERE study would be deferred based on “regulatory commentary” that apparently influenced the investigators to decide to wait for the IMpress data. Translation: the FDA. It would be instructive to know if they plan to wait for partial or complete study data. bp

[kmall]

Bp - Hopefully Dr. Scarlett might address that question during the next CC and elaborate on any "Regulatory commentary" he can provide (ie; TLS issues you had mentioned). I will add that Aron Feingold is definitely on the ball. Not only did she respond in a timely manner, but she had Geron IT update their website to reflect that correction within 3 business days of my inquiry. She's a welcome addition to the team as far as I'm concerned.

From what I can gather, and only an outside opinion of course, Geron is quietly getting their ducks in order for a "full steam ahead assault" towards commercialization once approval commences. Between the uptick in hiring, internal promotions, being proactive with Regulatory agencies prior to an NDA MA submittal and the manufacturing and certification of facilities producing Imetelstat being in order, it seems that they are following up with any "unforseen" set backs and roadblocks which may delay the entire process. Another interesting note is the latest position being advertised:

Senior Field Medical Liaison - Southeast Territory

Breaking these positions down into "territories" infers that a mass marketing national rollout will commence once approved. The Big Pharma backgrounds of these "newly hired employees" has given Geron an upper hand in problem solving and strategic planning in the pre-approval process of Imetelstat. I think Dr. Scarlett summed it up best back in May 2019 at the Needham Healthcare Conference:

“We could have skimped and watched our pennies but when you have a Phase 3 drug in this business chance favors when you invest in the drug and people, and that is what we have decided to do.” - Dr. John Scarlett

I think as we close in on TLR in January, we need to reflect on the above statement more and more, while being thankful as investors that Dr. Scarlett hasn't been penny pinching these past four years. -Kmall

[biopearl123]

Kmall, it is extremely unlikely that Dr. Scarlett will comment on any guidance from the FDA except in the most inchoate way. He has always been careful in this regard. Unfortunately this speaks to the power and fear the FDA wields over companies. Perhaps that’s a good thing in the end as it certainly prevents companies from getting out ahead of themselves and potentially misleading stockholders and patients. I think Geron has been very careful this regard. As to Aron. High marks indeed. As you point out, this last posted position indicates a regionalization of sales and medical support and suggests a large marketing effort to come. They plan to do it right, right from the start. A while back I was a physician consultant to Medtronic. That’s how they did it. Regards, bp