Here's text of Max Gomez interview of Dr. Ji released by Vatican today.
"Few companies have as large a presence in the small molecule therapeutic and diagnostic
space as Sorrento Therapeutics. Henry Ji, Sorrento's president and CEO, joins us now to
discuss their technology.
Max Gomez, PhD:
Henry Ji, chairman and president and CEO of Sorrento Therapeutics, welcome. Henry, this
is really an exciting time for your company and in research here in general. I know that
Sorrento is involved in diagnostics, prevention, early intervention, rescue therapies for a
variety of different diseases if you will, but let's talk about the hot one at the moment. What's
your approach, a comprehensive solution if you will, for COVID-19?
Henry Ji, PhD:
So, hey, thanks, Max. And our solution to it is detect early, treat timely. Treat timely means
that at different stages of COVID-19 disease, you treat with different measures or treatment
solutions. So, for example, we have the COVID-19 rapid antigen detection system called
COVISTIX, and we can detect whether you have the infection in as short a time as 2-5
minutes. Moreover, if your test remains negative for 15 minutes, you can proceed with your
normal activities. With COVISTIX, we can detect virus in patients between symptomatic
days 1 and 7. The moment you have symptoms, you say, "Okay, I’m infected. Now what's
the solution? What’s the next step?" The next step in treatment of infected individuals we
are developing at Sorrento is a neutralizing antibody. Neutralizing antibody treatment is
among the most effective ways to treat the COVID-19 infection because the antibody binds
and prevents viruses from entering cells, which potentially results in decreased virus
replication and spread within an infected person.
We are developing three ways to administer neutralizing antibodies. One way is to deliver
the antibodies by IV. Our IV administration is designed to require only 2-5 minutes, which
will conserve the hospital resources currently required for one hour or five hour infusions.
The idea is to provide treatment solutions that are easily delivered in an outpatient setting.
Our second form of neutralizing antibody administration currently in clinical trials makes use
of nasal drops. This allows direct delivery of the antibodies into your nose, blocking the virus
entry into the cells of the epithelial layer in the nose, and potentially inhibiting viruses from
replicating in this area and spreading into other regions of the respiratory tract.
A third means of delivering neutralizing antibody to patients currently in development at
Sorrento is by injection of a DNA plasmid encoding the antibody into your muscle. The cells
that make up your muscle would then express the neutralizing antibody in your body. We
are currently completing work supported by government contracts for this this program.
DNA-encoded antibodies provide a very rapid means of addressing the treatment
challenges posed by emerging variants of concern during a pandemic. Public health officials
are focused on the worldwide circulation of virus variants of concern first identified in the
UK, Brazil, South Africa, and India. We recently finalized an exclusive licensing deal with
Mount Sinai to co-develop antibodies that cover each of the known variants of concern. We
are combining the neutralizing properties of antibodies discovered at Sorrento and Mt. Sinai
to develop a cocktail of two antibodies in each of our three delivery systems for treatment of
infected individuals.3
Max Gomez, PhD:
Henry, let me ask you the diagnostic part of it. How was that administered? What do you
use for that now?
Henry Ji, PhD:
Oh, the test is very simple. You do a quick nose swab. It's not a deep nose swab, but rather
shallow. You then place the swab into a lysis buffer and pour the resulting mixture into a
detection cassette. The test provides your positive or negative result within a few short
minutes.
Max Gomez, PhD:
So you mentioned also then that this cocktail that you're testing, that can be administered a
variety of different ways. How is it that this can cover all of the different variants then, since
we keep hearing that the variants are very specific for the vaccines? How is it that this
covers the different variants?
Henry Ji, PhD:
Because we have tested our antibodies for neutralizing activity against the variants. We
have each of the viruses considered variants of concern, or VOCs, and we have their
respective Spike proteins expressed as a recombinant protein. If any antibody in our
collection binds and neutralizes one or more variant of concern, we can use that antibody
as a component of a two-antibody cocktail that provides coverage against all of the virus
variants of concern. We are already pushing a cocktail through development that potently
neutralizes each of the known variants of concern. This cocktail contains two antibodies,
STI-2020 and STI-5041, and these two antibodies provide potent neutralizing coverage for
all of the currently identified VOCs. We know the virus will continue to evolve as infection
numbers increase, so we are focusing our efforts on developing a full panel of antibodies to
potentially provide coverage against future virus variants.
Max Gomez, PhD:
And as new variants pop up, do you manufacture these new antibodies or how do you then
decide what to put into the cocktail?
Henry Ji, PhD:
We believe right now we have an antibody cocktail that provides potent neutralizing activity
against each of the current variants of concern. Manufacturing of the antibodies in this
cocktail is ongoing. As new variants emerge, we will continue to monitor for gaps in
coverage by our antibody cocktail and explore new antibody combinations from our current
collection of preclinical candidates to address those gaps. We can initiate manufacturing
activities for any antibody in our collection within weeks, and we can use this capability to
enable our antibody delivery systems and meet the treatment challenges associated with
any emerging variants of concern. Our treatments and diagnostics for mild and moderate
COVID-19 will include those that you could access at your local pharmacy and those that 4
are administered in an outpatient setting. Our vision is to allow those who receive a positive
COVISTIX result to access COVIDROPS or COVI-AMG neutralizing antibodies to treat their
infection.
It’s worth mentioning here our work on therapeutics for use in treatment of moderate to
severe COVID-19 cases in the ICU. Oral administration of Abivertinib, a Bruton’s tyrosine
kinase inhibitor, is designed to decrease the effects of cytokine storm in the context of
COVID-19. We are currently conducting Phase I clinical trials with Abivertinib, and we have
enrolled over 300 patients in both U.S. and Brazil, thus far. We are also in discussions with
the government of Mexico around extension of these trials into hard-hit regions of the
country. We are working to determine if Abivertinib can help to more quickly discharge
COVID-19 patients experiencing moderate to severe COVID-19 from the hospital. In clinical
situations where ICU patients require oxygen and intubation on the ventilator, Sorrento is
investigating the clinical safety and efficacy of treatment using adipose-derived
mesenchymal stem cells. To date, each of the ten patients who has undergone this
treatment, which requires three infusions, has been discharged from the ICU. After the first
infusion, many of the patients’ conditions improved; they reported feeling much better and
they required less supplemental oxygen. After the third infusion, some patients were
immediately released from the hospital. We're talking about patients being discharged from
ICU and discharged from hospital on the same day. Very impressive.
Max Gomez, PhD:
This sounds obviously very exciting. And it sounds like you have the capability to develop
some of this for other viruses or even other diseases, infectious diseases, and going on to
cancer. How else will you use this platform?
Henry Ji, PhD:
We have taken a human antibody library approach. This approach does not require the use
of recovered patient samples. Rather than relying on B cells isolated from infected patients
to identify candidate antibodies, we can use our molecular libraries that already encode
billions of antibodies to screen potentially neutralizing antibodies for any pandemic threat
pathogen target.
Let's say that in response to an actual outbreak or as part of a pandemic readiness
program, a decision is made to develop antibodies that neutralize Nipah virus. We can
screen against Nipah virus proteins and isolate candidate neutralizing antibodies within a
two-week timeframe. These antibodies can be developed as traditional protein therapeutics
or we can encode the antibody sequences on DNA plasmids for intramuscular
administration. DNA plasmids of this type can be manufactured very quickly, and within a
month we could have a therapeutic ready for use in the clinic. This type of rapid response
capability is aligned with the mission at DARPA and they have supported us with a contract
to develop this technology as a COVID-19 response that could readily translate into use for
protection and treatment of existing or emerging pandemic threat pathogens.
Of course, this technology can also be used for protein therapeutics in the oncology and
metabolic disease spaces. Use of DNA plasmid-based technology to express immune
checkpoint inhibitors or enzyme replacement therapies would provide innovative options
over the established use of manufactured protein for these purposes.
Plasmid DNA directed expression of biological therapeutics in patients can be a novel and valuable
means of achieving long-term treatment solutions while minimizing the burden of treatment
on patients and health care providers.
Max Gomez, PhD:
You have so many different possibilities here within the company, how do you decide what
to focus on? You know, the saying that a Jack of all trades is a master of none. How do you
decide where to really put your energies as a company?
Henry Ji, PhD:
We have a great deal of energy and drive at Sorrento. We have a healthy portfolio of
projects and strong support from public equity, cash holdings, and government contracts to
support multiple ongoing efforts to bring products to market. This has allowed us to develop
products that are now at various stages of clinical development. On the diagnostic side, we
have already submitted our EUA for COVISTIX. If the FDA give us a green light to proceed,
we are ready to enter the market, which should provide us a revenue stream. Our
neutralizing antibody is currently in Phase 2, as is Abivertinib, and our mesenchymal stem
cell therapeutic. EUA approval around any one of these programs will serve to further
increase our revenue and fuel our push to master the trade of developing therapeutic and
diagnostic solutions across a wide selection of human disease areas.
Max Gomez, PhD:
So you can chew gum and walk at the same time.
Henry Ji, PhD:
Exactly. That's the plan.
Max Gomez, PhD:
Henry Ji, thank you so much for your time. It sounds very exciting."
