Thanks to @DMac for identifying this: A new podcast interview with Joan Mannick, Tornado Therapeutics (a rapalog developer). I find it a little sad that when the interviewer asks “what’s the trouble with rapamycin…” Joan’s response is “The problem with rapamycin is it has no patent-life left…” (i.e. nobody can make much money off it, so there is no incentive to do all the clinical testing required to prove its efficacy in lifespan improvement).
Joan Mannick, CEO and co-Founder of Tornado Therapeutics, joins the podcast to discuss her company’s exciting mission of developing a new generation of rapalog compounds specifically targeting the TORC1 complex. Rapalogs are analogs of the natural compound rapamycin, which has been shown to extend lifespan and healthspan in animal models by inhibiting the TOR pathway. However, rapamycin has limitations that have prevented its widespread clinical use for aging-related conditions.
Tornado aims to overcome these limitations by developing a portfolio of novel rapalogs licensed from Novartis, which were specifically designed to be more selective TORC1 inhibitors with improved drug-like properties relative to rapamycin. Early data suggests these compounds may have an improved safety profile and remain effective at treating diseases like cancer.
In her conversation with host Chris Patil, Dr. Mannick provides an accessible overview of TOR signaling biology and shares insights from her extensive experience developing rapalogs. The discussion covers Tornado’s strategic approach to indications like oncology and viral infections, the process of characterizing their licensed compounds, and notable milestones on the horizon.
Dr. Mannick provides an insider perspective on a compelling longevity biotech company striving to translate the promise of rapalogs into effective medicines for age-related diseases.
Key topics:
An overview of the TOR signaling pathway, the TORC1 and TORC2 complexes, and how the natural compound rapamycin inhibits TOR function.
The benefits and limitations of using rapamycin/rapalogs clinically, and the need for more selective TORC1 inhibitors with improved drug properties.
Tornado’s licensing of novel TORC1-specific rapalogs from Novartis, including early safety data.
Indications that Tornado is initially pursuing, including oncology and viral infection, applying lessons learned about rapalogs over the past decade.
The experience of being a “pipeline company” within the Cambrian Biopharma family, and the synergies available to companies operating within this model.
Love to see Dr Mannick working on developing new drugs. Her human trial with flu vaccine + everolimus was the thing that finally convinced many that rapalogues could be good for immune function and not just immunosuppressants.
Using a “youthful” mTOR model as a template to replicate is a nice start! Her comment that in our youth, mTOR is inhibited while we fast, but not as we get older. Getting short half life rapalouges that we may take at night while fasting seem to be a logical next step.
Thank you! I am tempted to switch to Everolimus because of that. I was thinking Dr. Mimmick was suggesting a rapalouge with an even a shorter half life. It could be taken at night while fasting and at low levels by the morning with hopefully no mTORC2 effect. She would be a good interview for @Krister_Kauppi.
Probably… that is true, but its going to be 4+ years before we might potentially be able to get our hands on any new compounds that Tornado Therapeutics is coming out with… so perhaps we use what we can get in the mean-time?
Yes - and they are targeting oncology and viral respiratory track infections for the initial indications for the drug… so I wouldn’t be surprised to see pricing (when not covered by insurance) in the $10,000 to $20,000 per month range, similar to the pricing of the other mTOR inhibitor Everolimus. (example below from GoodRx.com)
In all the presentation JM has made since CEO of TT her main point is always IP products for investment.
Do you really think you will have a “new” mTOR1 compound for a few hundred {and the average person could not afford that much] a month?
It will cost several thousands{on the inexpensive side] per month, these are businesses looking for minimum of hundred of millions a year in profit.
Investment into these companies are not for the benefit of humanity, any company stating such is premier BS. They want a compound wth long term IP protection.
Yes, this was a really great episode with Joan Mannick! I have started to prepare for the interview with her this autumn so if someone has any good questions just let me know.
One thing that she said that @David also pointed out was that fasting in elderly seems not to have good mTOR inhibition effects. Does there exist any study on this? I would really like to look into that.
I think Joan Mannick’s mission is very interesting and one day the IP for the great rapalogs will not be valid anymore and after that we in the longevity community can start using it at a reasonable price. Even if this is frustrating that it will take like 15-20 years before that I think it’s good that she moves the field forward. If we look at the rapamycin field it goes very slowly forward. If we want to increase the speed here we need to make it community driven. We can not rely on other researchers or companies to do the job that we want to be done. One thing that I have learned in life is to not wait for other people to solve your problems and destiny. It’s better to be the one who takes initiatives and creates the destiny that you want.
I agree that we are not the waiting type but we could accomplish so much more if we start working as a team in trying to move trials and research forward.
@Krister_Kauppi - Question of interest would be if we have a way or potential way of measuring mTOR activity. This may help clear up dosing end points rather than drug levels. Also a follow up question on actionable models such as trying to mimic youthful mTOR modulation vs. optimizing in another way such as short acting inhibitors at supra physiologic levels.
@Krister_Kauppi Thanks for asking. Regardless of your guest, I am interested in any way to measure yes/no and magnitude of effect of turning down mTOR (but not too much) and turning up autophagy (but not too much). Since we don’t have a good biological aging calculator yet, is there a smart way to estimate progress along the 9-12 hallmarks of aging in aggregate using, perhaps, chronic inflammation as a key indicator of improving immune function, turning down SASP, and engaging autophagy/mitophagy for cleaning up old, poorly functioning organelles? If inflammation is a good marker, how to best measure it? I’ve heard CRP is not a good measure.
From recent paper, link included here:
“Indicators of inflammaging, including elevations in cytokines IL-6, CRP, and TNF-a, are associated with all-cause mortality, as well as with a number of age- related chronic diseases, including cardiovascular dis- ease, diabetes mellitus, cancer, frailty, and sarcopenia.”
There are a lot of potential todos in the Rapamycin field which we can work together to move it forward in a better way.
Here are for example some
Setting up a Rapamycin fund in which we gather money to invest in different Rapamycin trials and research studies. We could also finance custom ITP:s. It costs around 450 000 dollars per intervention that we want to test.
Setting up our own rapamycin trials
We should consolidate all our data on rapamycin in a good way. Now the data is everywhere and it’s very hard to make comparisons between groups or people.
Create a good standard test kit. Pre rapamycin and during taking rapamycin. Helps also with comparison between people if we have a standardized way of doing this journey.
Setting up group self experiments. For example during a period a group tries to combine rapamycin with a specific intervention. Which is evaluated if it has synergistic, additive or detrimental effects.
Setting up a team around the Rapamycin podcast and improving it even more. There are lots of todos here
Start a world wide rapamycin longevity clinic.
There are lots of more potential todos. Together we can accomplish so much more if we start collaborating and doing things together.
