JNJ-74856665........"miracle drug trial?"

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kmall
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JNJ-74856665........"miracle drug trial?"

Post by kmall » Sat Sep 10, 2022 9:36 am

"Kevin" on the YMB provided this link yesterday:.

https://www.dailymail.co.uk/health/arti ... trial.html

Inside of the thread attached to that link "darell" replied with JNJ-74856665

Not quite sure where darell from the YMB got this info - Drug: JNJ-74856665 ?

There is a CT location in the UK for JNJ-74856665 at the Christie Cancer Centere, where this patient, Eliana Keeling, was treated.

23 study locations.....3 here in the US and 4 in the UK:

United Kingdom
Leicester Royal Infirmary
Leicester, United Kingdom, LE1 5WW

University College London Hospitals
London, United Kingdom, NW1 2BU

Kings College Hospital
London, United Kingdom, SE5 9RF

The Christie Nhs Foundation Trust
Manchester, United Kingdom, M20 4BX

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

"Detailed Description:
This is first-in-human (FIH) Phase 1, dose escalation study of JNJ-74856665 alone or in combination with Azacitidine or Venetoclax in participants with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS). Participants with Chronic Myelomonocytic Leukemia (CMML) are also eligible and will either receive JNJ-74856665 as monotherapy or in combination with Azacitidine......"

"AML. JNJ-74856665 is an orally bioavailable, potent, and selective dihydroorotate dehydrogenase (DHODH) inhibitor that binds to the enzyme's ubiquinone binding site promoting AML/MDS differentiation as well as cell cycle arrest and apoptosis."

*Drug combination treatments in Oncology are rapidly expanding, and even according to this article, not every patient responds equally.

"'Dr Emma Searle, consultant haematologist at The Christie, said: 'Eliana had a poor prognosis and her only chance was the clinical trial and bone marrow transplant for long term survival.

'We're really pleased Eliana had such a good response and is now leukaemia free.

'Given she had a very limited life expectancy when the chemotherapy failed to work, this is an excellent result for her.

'Not all our trial patients who have AML respond as well as Eliana did, but we are grateful to every patient and relative that feels able to support research here at The Christie.

'Trials are so important to make progress in treating cancer'"

**It is also important to note that according to the article, Eliana Keeling had a strong will to live and was a "regular gym-goer." Being physically fit with a healthy mental attitude can be essential in a possible successful treatment as well.

Nice dig by both Kevin and darrell. Thank you for providing this information! -Kmall

LWS
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Re: JNJ-74856665........"miracle drug trial?"

Post by LWS » Sat Sep 10, 2022 3:23 pm

JNJ-74856665 --- miracle drug?

I am not sure what this means. Are you suggesting that Imetelstat is somewhere in this combination (or should be, or could be)? I am not very good at reading between the lines.

The keyword seems to be "apoptosis" or death of the cancer-stem-cell.
"AML. JNJ-74856665 is an orally bioavailable, potent, and selective dihydroorotate dehydrogenase (DHODH) inhibitor that binds to the enzyme's ubiquinone binding site promoting AML/MDS differentiation as well as cell cycle arrest and apoptosis."
For Reference:

Imetelstat Induces Leukemia Stem Cell Death in Pediatric Acute Myeloid Leukemia Patient-Derived Xenografts - PMC (nih.gov
)
Last edited by LWS on Sat Sep 10, 2022 6:34 pm, edited 3 times in total.

biopearl123
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Re: JNJ-74856665........"miracle drug trial?"

Post by biopearl123 » Sat Sep 10, 2022 5:10 pm

Kmall, thank for posting this. I think it is an important reminder that our universe here on the board is a small and concentrated one. There are many other drugs out there worth keeping track of that are doing well and helping patients, some of which are oral but perhaps in earlier stages of development. Imetelstat thus far appears to remain unique in being able to selectively target the malignant clone and CSC but many other potentially effective approaches are also in development. We will also see that specific molecular/genetic signatures may predispose to more efficacious responses of one drug over another. Combination therapies with these agents continue the search for the magic bullet(s).

kmall
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Re: JNJ-74856665........"miracle drug trial?"

Post by kmall » Sat Sep 10, 2022 9:22 pm

@LWS - No. There isn't any suggestion here of Imetelstat. This is a totally separate drug:

"JNJ-74856665 is an orally bioavailable"....in other words "a pill."

Apparently, this particular combination treatment "cured" this patient, since she received a bone marrow transplant back in December 2021 and is in remission for now.

There are several interesting takes from this article that could relate to Imetelstat in combinations as well.

*Again, not certain if JNJ-74856665 is the "miracle drug" described in the article, but from the Clinical Trial.gov website, there seems to be a strong possibility.

1. JNJ-74856665 is being used in this study for AML in combination with Azacitidine or Venetoclax.

Imetelstat will be used in combination with Azacitidine or Venetoclax in the upcoming TELOMERE P1/2 Clinical Trial, and is expected to be open for patient enrollment in the second half of 2022.

2. Both JNJ-74856665 and Imetelstat are ground breaking new drugs in cancer treatment.

3. Eliana Keeling, the patient in the article was very ill and told at one point she had 2 months to live. Imetelstat has been used for very ill patients in prior Clinical Trials.

Now remember, Eliana Keeling is one patient of 157 participants. She was very active prior to being diagnosed, on the low end of patient age average for AML, and she had excellent mental fortitude to deal with the anguish associated with her diagnosis. All of that plays a very important part in a successful outcome.

However, as Bp has pointed out in this thread, there are many new drugs under development at the moment targeting Hematological disorders. Imetelstat and Geron do not stand alone, and competition in the space is ramping up. Although I firmly believe that Dr. Scarlett and his team have the ability of going it alone, there are an inordinate amount of challenges to overcome if that is the road they ultimately pursue. 2030 will be a much, much different landscape than today, and going it alone isn't as easy as some may have you believe. -Kmall

LWS
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Re: JNJ-74856665........"miracle drug trial?"

Post by LWS » Sat Sep 10, 2022 11:17 pm


Kmall--- thanks for all of the inputs.


JNJ continues its interest in Imetelstat. There are several pieces to this puzzle and we don't quite know how they fit together. Imetelstat is one of those pieces. JNJ and AbbVie (Azacitidine or Venetoclax) continue to be important collaborators, and perhaps more. The 3 conferences this week, hopefully, will help us understand what is going on.

Here are some of the pieces to the puzzle
*Again, not certain if JNJ-74856665 is the "miracle drug" described in the article, but from the Clinical Trial.gov website, there seems to be a strong possibility.

1. JNJ-74856665 is being used in this study for AML in combination with Azacitidine or Venetoclax.

Imetelstat will be used in combination with Azacitidine or Venetoclax in the upcoming TELOMERE P1/2 Clinical Trial, and is expected to be open for patient enrollment in the second half of 2022
-----------------------------------------------------------------------
JNJ has been part of Geron's past. JNJ will likely be involved in Geron's future.

The Lymphoid Malignancy studies at MD Anderson will add quite a bit to that answer. As will P3 IMerge TLR in January and hopefully FDA NDA to follow.

If some Big Pharma doesn't step up to the plate soon, this could easily be out of their reach in the very near future. Just my take on how I see things these days. -Kmall

(From kmall)----Nishan Sengupta - Vice President, Market-Access, Pricing, Evidence Strategy, Geron Corporation

Hired August 2021: Nishan Sengupta Is CURRENTLY employed at JNJ as well as Geron. He had been employed at JNJ for over 17yrs.

Nishan Sengupta's CURRENT title at JNJ is: Global/US Access Strategy Lead-IMBRUVICA, B-Cell, Rare Hem - August 2019 - PRESENT

------------------------------------------------------
JNJ's continuing interest plus MD Anderson's ongoing research is now in focus. Imbruvica is a JNJ approved medicine and would seem to be a logical combination with Imetelstat. JNJ has been the 'mystery-man' for a very long time.

What is IMBRUVICA® (ibrutinib)?


IMBRUVICA® (ibrutinib) is a prescription medicine used to treat adults with:
• Mantle cell lymphoma (MCL) who have received at least one prior treatment
• Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL)
• Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion
• Waldenström’s macroglobulinemia (WM)
• Marginal zone lymphoma (MZL) who require a medicine by mouth or injection (systemic therapy) and have received a certain type of prior treatment
• Chronic graft versus host disease (cGVHD) after failure of 1 or more lines of systemic therapy

kmall
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Re: JNJ-74856665........"miracle drug trial?"

Post by kmall » Sun Sep 11, 2022 2:33 am

@LWS - Once approved for a single indication, I would imagine Imetelstat could then be eligible for use in various Clinical Trial situations or in conjunction with other approved drugs in the field.

Not quite sure how all of that plays out or a timeframe from approval to additional combinations - or if those combinations of approved drugs need to pass some sort of safety CT for dosage and possible side effect issues?

Another point to add to the IMBRUVICA® (ibrutinib) list you've posted here is that Dr. Rizo was instrumental in the development of IMBRUVICA® (ibrutinib) while at Janssen:

"Dr. Rizo was Global Clinical Leader for the ibrutinib mantle cell lymphoma (MCL) program and was responsible for all MCL studies led by Janssen." -Kmall

Bridge to Sell
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Re: JNJ-74856665........"miracle drug trial?"

Post by Bridge to Sell » Mon Sep 12, 2022 3:09 am

It’s far more likely that Imetelstat could be prescribed off label ‘in the field’ as a single agent than it would be in conjunction with other drugs. The Phase 2 and 3 trials have established dose escalation, efficacy and side effects as a single agent. For combined use with something as simple as Ruxolitinib, clinical trials are required to ensure no unwanted side effects occur. Without such data, I can’t imagine any doctor ever prescribing Imetelstat in an untested combination with another drug.

kmall
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Re: JNJ-74856665........"miracle drug trial?"

Post by kmall » Mon Sep 12, 2022 1:28 pm

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

LWS
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Re: JNJ-74856665........"miracle drug trial?"

Post by LWS » Fri Sep 23, 2022 8:20 pm

the combination of JNJ-74856665 with Azacitidine or Venetoclax, has so far proven successful as a "miracle cure" - cited in the article. -Kmall


Is there any follow-up? What is in the rest of the combination (a secret?). The term "miracle cure" is certainly eye-opening.

kmall
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Re: JNJ-74856665........"miracle drug trial?"

Post by kmall » Fri Sep 23, 2022 11:46 pm

@LWS - The patient, Eliana Keeling, suffering from AML, who was cited in the article went from having a 2 month life expectancy, to being treated with a combination of JNJ-74856665 with Azacitidine or Venetoclax - or so we presume.

Remember that JNJ-74856665 is never mentioned in the article. However, the JNJ-74856665 combination Clinical Trial is located at the same hospital where she was treated, and the article does mention a Clinical Trial which she was a part of at that location.

Also, keep in mind that the success of this combination enabled her to be eligible for a bone marrow transplant.....hence "the cure" part.

As of the writing of the article she was in complete remission. So for now it seems that this particular combination worked for this individual patient in order to get her to become healthy enough so that a transplant could be performed.

I don't think that any "secrets" are being held here. But there is always a possibility that JNJ-74856665, an orally bioavailable, potent, and selective dihydroorotate dehydrogenase (DHODH) inhibitor has another name already in a completely different form. -Kmall

LWS
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Re: JNJ-74856665........"miracle drug trial?"

Post by LWS » Sat Sep 24, 2022 4:25 am

Azacitidine is designed to slow the production of leukemia cells and help the bone marrow produce more healthy and normal functioning cells. Venetoclax is designed to kill leukemia cells by binding to and inhibiting a protein in cancerous cells that prevents the cell from dying known as “BCL-2”
To Kmall--JNJ-74856665 has some other ingredients. You talk about "always a possibility". I am not sure what you mean. Also, the phrase "in a completely different form" is intriguing.
But there is always a possibility that JNJ-74856665, an orally bioavailable, potent, and selective dihydroorotate dehydrogenase (DHODH) inhibitor has another name already in a completely different form. -Kmall

LWS
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Re: JNJ-74856665........"miracle drug trial?"

Post by LWS » Tue Feb 07, 2023 5:15 pm

The 3 medicines that have been proven as cancer cell killers are Venetoclax (approved --AbbVie), Imbruvia (approved -- JNJ), Imetelstat (not approved -- Geron).

Are there any updates on JNJ-74856665?

Imetelstat needs to get approved (single-agent) 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).
------------------------------------------------
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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