I had a good college dream the other day. Instead of one of
those college nightmares when you find out that you wrote down the wrong date
of the final on the day of the final. Oops Or did that really happen? I think it did and
I think it happened more than once. Last night I dreamt that I decided I was
going to go back to school for biology. Jeremy was really happy for me, he
thought it was a great idea. The dream was pre Jonah and we still had the rest of our
lives in front of us. In my dream I was so relived, I felt great.
Our dreams reflect what’s going on in our waking life. Sri and I had some very ambitious plans to
submit two NIH grants. While writing the
grants the score from our previous grant round came back. Two out of three of the
reviewers gave us great scores, reviewer # 1 however gave us a horrible score.
His/her comments were the exact opposite of the other two reviewers and way off
base.
Sri dropped everything to write a rebuttal, because of COVID
the NIH gave everyone extensions on grant submissions which were lenient enough
to allow us to resubmit our grant during the current grant period. In layman’s
terms we would have normally had to wait until June to resubmit. The other two
grants were finished and submitted on the due date. Even after the NIH gave us
a six-week extension we still got the grants submitted on the day of.
I’m actually starting to get used to the last-minute thing. When
you’re working with a half a dozen collaborators, very busy collaborators that
are working on the assumption that we ‘might’ win the grant. There isn’t a ton
of incentive for our collaborators to bust their butts for a we might win. My scientists did an awesome job collaborating and pushing drafts back and forth adding and revising, it's just a lot of people and institutions to work around. I
hold my breath and hope for the best. That was last week.
This week our comments were due back to the FDA in response
to a draft guidance for industry on Sanfilippo drug development: “Mucopolysaccharidosis
Type III (Sanfilippo Syndrome): Developing Drugs for Treatment Guidance for
Industry”. The guidance is advice to industry on what the FDA would like to see
industry follow while designing their drug trials.
At first, I was super excited that the FDA was taking the
time to address Sanfilippo, we’re an ultra-rare disease and they were actually
thinking about us. The opening was pretty straight forward, no grievances
there, as I read deeper, I became perplexed, reading further, my heart started
pounding. I thought WTF is this shit. Not having ever read an industry guidance
before. There were some blatant inaccuracies and I was disturbed that the
guidance covered all 4 subtypes of Sanfilippo but hardly said anything about
IIIC or D, as if we didn’t exist. Towards the end of the guidance it suggested
that industry should have a randomized, parallel group trial design with an
appropriate concurrent control group. The tears welled up in my eyes, I couldn’t
believe what I was reading. In layman’s terms, this meant that out of 10 kids
in a trial that 5 of the kids would be receiving placebo. I panicked- this one
line became my full focus of the entire document. My mind envisioned the worst,
here I am the sponsor i.e. ‘industry’ conducting the trial and I’m going to
have to tell the parents that I have known for 10 years that half of their kids
would be receiving drug and the other half wouldn’t. That’s just one thought.
What about the families that have siblings in the trial, one child receives
placebo and the other drug? Furthermore, these are not simple trials, they’re
extremely invasive and there is a lot of risk involved. In some instances,
families will have to move to the trial site, or travel back and forth with
their kids for a couple of years. Lastly, It’s a huge financial and emotional
burden on the families. Who’s going to participate in a trial, knowing all the
risk?
Mari sat at her desk watching me go through my emotions first
elated then heart broken, the phone rang, Mari said it’s Cara. Cara was just as
dumbfounded as I was. We talked out our game plan, WORLD was in a few days, we’d
have the opportunity to see all of our key opinion leaders, including pharma and
our doctors. The Cure Sanfilippo Foundation pulled together a last-minute
meeting with all the major stakeholders. I called my go to advisor.
She answered the phone on the first ring, “Jill….. I know
why you’re calling. Don’t worry this is a boiler plate guidance, the FDA has to
say that. This is our opportunity to tell the FDA how the guidance should read.”
I jumped down from the ledge and re-read the guidance. I
read it over and over, I know it by heart. Our stakeholder meeting in Florida went
really well, it was inspiring to see half a dozen competing drug companies
sitting at the table with parents and our physicians. Remember there is A and B then there is C and
D. A and B are more prevalent and therefor receive more pharma attention.
Phoenix Nest is the only company working on a treatment for C and D.
WORLD is a huge conference with thousands in attendance from
around the world, the focus is on lysosomal storage disorders. It is always
held in February, this year it was the 9th-13th. On my flight to FL, I noticed that the snow-birders
were wiping down their seats and tray tables. Not unusual thing to do but they
were ALL doing it. While in Florida I got a text from Mari, her boyfriend had
just picked up his first COVID body. Mari’s boyfriend runs a mortuary in Queens
with his dad. I asked my doctor friend what COVID was, she replied some flu
going around. I thought about the grannies on the plane wiping down their
seats. On the way home they were doing it again, I gave the women next to me my
puppy dog eyes, and she offered me a wet wipe. Relieved I wiped everything
down.
Once home I was so busy working on grants and preparing for
my FDA talk, I completely ignored the news happening around me. Mari kept
bringing COVID up and my upcoming travel plans. I ignored her. Off to the FDA
on Amtrak, I had a speaking engagement that I had been stressing over for weeks.
I was still a bit bitter about the Sanfilippo guidance, the writers of the
guidance were also the organizers of the workshop. I did not hold back in my talk,
the organizers said I should be open and honest, tell it like it is. They sincerely
wanted to hear how they can help the ultra-rare community. I believe them too.
During the months before my workshop there had been several other workshops on
the same topic, but from different angles. I knew of a couple of closed-door
meetings as well. After my talk, Dr. P.J. Brookes spoke and for the first time
we heard publicly what the FDA and NIH were planning and had actually just
executed. I left the workshop inspired, the FDA was listening, and I just got
my chance to add my two cents. I was thanked profusely by FDA officials, they
whispered to me that my talk was exactly what the FDA needed to hear. One of
these guys knows that I have no filter.
My main grievance that I spoke about was the disparity
between a rare drug and an ultra-rare drug. The Orphan Drug act was passed into
law in 1983, at the height of the AIDS pandemic, the ODA did a bang-up job incentivizing
pharma to create drugs for HIV. Remember how scared we were of AIDS, curious
are you just as scared of COVID? In the US HIV was still considered a rare
disease. We hadn’t been hit as hard as other countries. The ODA gives pharmaceutical
companies 7 years of drug exclusivity, meaning a generic drug can’t come out
and compete with them. I think it is commendable that GILEAD gave back its
Orphan Drug Designation, they knew it was unfair, COVID would soon surpass the
definition of a rare disease.
There are 7,000 rare diseases, a rare disease in the US is
defined as having a patient population of 200,000 or less. MPS IIIC has 20 known patients in the US.
Think on that. If you’re a drug company what disease are you going to choose to
make a drug for?
This is why I created Phoenix Nest, 10 years I have been
doing this. In those ten years I have not had a company offer to partner with
me, or a VC want to fund my company. I shared this with the FDA. I told them
that the Orphan Drug Act needed to be updated. That they needed to officially recognize
ultra-rare diseases and while they’re at it to recognize uber-rare diseases
too. The categories need to have incentives that fit the disease patient population.
Parents should not have to be the people
driving the science. I have de-risked everything for pharma to come and
commercialize our drug, yet MPS IIIC and D still don’t interest them. Our drug
is extremely expensive to maintain, and they don’t think the return will be
worth it.
Let’s get real, pharma can pick a rare disease and get the
same incentives and make a ton more money. My disease has another problem too, it’s so
slow to progress that sponsors don’t want to wait around long enough to prove
to the FDA that the drug works. This was another topic that I highlighted in my
talk and another opportunity to create incentives for. Of course, the FDA just can’t snap their
fingers and give diseases like mine a fair chance. It takes an act of congress.
I’m not directly asking for taxpayers’ dollars to go to uber-rare diseases, I’m
asking for more federal dollars to go to the FDA and NIH, so that the FDA and
NIH can hire more people to support the extra workload that I’m asking for them
to do. Incentives can come in the form of FDA and NIH handholding, guiding
sponsors through trial design and lending their expertise. Lowering trial and
error risks and spreading out the workload.
On a side note, the scientists in front of me had their laptops
open to graphs and charts, they were whispering about the spread of COVID. Between
March and May I had three more work trips planned plus 2 flights to Oregon. The
moment I got home the emails started coming in everything cancelled and NY shut
down. At least COVID gave Sri and I more time to get our grants in. Tuesday was
the deadline for PN to submit our comments to the FDA regarding the guidance. Not
to mess with tradition, I got my comments in at 5:05pm on Tuesday.
I did miss one deadline. I promised to shave my head on the
5th for the #GivingTuesdayNow campaign. I didn’t have time, I had to
get the grants and FDA comments in. Not an excuse to delay the shaving, I said
I’d do it. I also wanted to write another blog telling all our supporters why
you should help me fund gene therapy for Jonah and his friends.
I finally feel in control of the development of our gene
therapy program, from the last dosage and tox study to designing the NH and
clinical trial. Moving from a site in the UK to UTSW in TX was the best thing I
could have done. My reasoning for sticking with Manchester was emotionally driven
and not practical.
After having our Pre-IND meeting with the FDA, I could no
longer lie to myself, I had to finish the job in the US. All the resources I
need to complete my job are right here. The FDA asked us to do another dosage
study with mice, there is no getting around that. Over the years I had been turning
to Steve Gray as an advisor, he was on our Pre-IND call too. Steve had asked me
before why I hadn’t had Brian create our AAV9 with a self complementary (SC) backbone
instead of a single strand (SS) backbone. The thought 8 years ago was that our
gene was too big to fit into an SC backbone. Steve begged to differ; it could
be done now.
When the FDA told us, we had to do a dosage study, Steve
brought it up again. Here is our opportunity to strengthen our vector. With the
help of Jude Samulski (Askbio) and Steve Gray’s lab we made a new vector. When I say we I mean
them I just said thank you. Then Sri and I found the companies to do the next dosage
study and a new tox study and the labs to turn the vector recipe into a drug. The
Cure Sanfilippo Foundation came through with the funds to get us started.
I’m really happy. I’m happy because I don’t have to depend
on a University to get the job done. We’re working entirely with contract companies;
I give them a job to do and they do it. We have a service agreement, no lawyer
involvement or having to license anything, all IP belongs to PN. I don’t have
to deal with PhD students quitting, or college breaks and vacation time off. Now, I have a representative that I can call
anytime for updates and I get them in a timely fashion. It’s so nice to work
with a good CRO. We’re making three plasmids from two different companies that
will be sent to a fourth company to combine the three of them and then sent to
the 5th company a vector facility to be attached to the virus and
scaled up. Everything has to be seamless. It is a massive amount of monitoring.
Good thing Sri and I never do anything last minute.
I need another $600,000 to conclude these studies and I don’t
know where it’s going to come from yet. I have my doubts that shaving my head
on Sunday, Mother’s Day will really inspire a $600,000 donation, one can hope. This
is also the week of Jonah’s MPS IIIC diagnosis. Ground zero, it’s officially 10
years now. In the beginning I had hoped we would have a drug through trial by
now. If I had the funding, we would have been. I don’t know how I feel about
this reality. I don’t think it’s unfair that I wasn’t wealthy when we had
Jonah. I don’t think it’s unfair that wealthy folks turn away, that is their prerogative.
I have had plenty of people help me with in kind services and
they’re the reason we have gotten this far. I’m mostly disappointed in myself
for not being able to find someone to invest. I haven’t tried hard enough; I hide
behind my blog and speeches, so I don’t have to look anyone directly in the eye
and ask for money. I’d rather do everything by myself then ask some nasty MBA
for an investment only to be told that they wouldn’t touch my disease with a
ten-foot pole. Note to self, I need to hire someone to do it for me.
The grant we resubmitted would lighten the load a little
bit, but Sri and I fear that the competition for NIH grant funding is going to
double now that COVID has wiped out our economy. Labs will be turning to grants
now that investors are tightening their purse strings. As for the future where
will the federal government be putting their resources? One can only hope that
our country will realize how important the FDA, CDC and the NIH are to us. Even
if the NIH continues to be funded as well as in the past, there will most
certainly be more competition. I can’t count on federal funds anymore.
For whatever reason I feel good, maybe it was the dream,
maybe it’s todays sunshine or the relief of our deadlines done. I feel good
because I have support. Not financial support but the support of brilliant and
compassionate people that want to help me and that is half the battle.
Speaking of the brilliant and compassionate people helping
me, here they are! A huge shout out to UTSW, Berge Minassian and Steve Gray,
Dr. Gray being one of the scientists that helped me redesign our vector to be
everything it can be and Dr. Minassian, the man that has offered up his team of
physicians to run our NHS and our gene therapy clinical trial. https://www.dallasnews.com/business/health-care/2020/04/29/with-30-million-in-funding-dallas-startup-will-speed-gene-therapy-clinical-trials/
After reading the article you’re going to ask me why Taysha
therapeutics hasn’t picked up MPS IIIC? Don’t think I haven’t tried, but
obviously I haven’t tried hard enough. The CEO of Taysha, RA Sessions II looks
like a nice guy, not the type to tell me my disease is too rare. Maybe Mr. Sessions
will catch the video of Jonah shaving my head on Sunday and come to the
conclusion that I’m not just another crazy desperate mother trying to save her child’s
life. That I’m completely rational and my son is totally adorable. Then he’ll
ask Steve and Berge if we’re worth the investment and they’ll vouch for me. Hoping
Jonah keeps his cool and doesn’t get overly excited, shave off my eyebrows and
cut off my ear. I am such an optimist.
Happy Mother’s Day Mom and good luck on your surgery! We can’t
wait to come visit you.
