"You're an entrepreneur, if ALS has no cure, find one"

Yossi Gross and Ariel Gordon Photo: Inbal Marmari

Ariel Gordon and Yossi Gross founded NeuroSense Therapeutics in response to family tragedies when ALS struck.

One day, Eti, wife of Israeli high-tech entrepreneur Ariel Gordon, complained of being unable to dance a third round of salsa. Gordon laughed and said, "Eti, I can't do the first round." Who knew that this banal exchange marked the beginning of a nightmare?

Serial entrepreneur and Rainbow Medical founder Yossi Gross, who scored a near $1 billion exit with Valtech Cardio, together with Amir Gross, his son, will not forget the day his sister came to him on Moshav Mazor, where their entire family lives, and told him that something strange had happened: her partner in her Saturday hikes, who usually lagged behind her, had overtaken her.

Gordon and Gross share an ALS family tragedy: a disease they had barely heard of before it became the center of their lives in more than one sense. ALS is an incurable degenerative disease that attacks the motor nerve cells. When these cells are damaged, they are unable to operate the body's muscles, which weaken until they are completely paralyzed. Within a few months, a completely healthy and active person, even an accomplished athlete, becomes isolated and hooked up to a respirator, with communication restricted to eyelid movements, and does not survive long.

Another thing that Gordon and Gross share is that each of them decided to search for a remedy. For Gross, whose sister died two years ago, it was a gesture for other patients. For Gordon, whose wife sends him WhatsApp messages that she wrote with eyelid movements during our conversation, it was almost like a Hans Christian Andersen story. They are both now investors in NeuroSense Therapeutics, founded two and a half years ago by CEO Alon Ben-Noon.

It takes time to diagnose ALS. It is a complicated disease with no clear biological sign; it is diagnosed almost completely by eliminating all other possibilities. In 2014, not long after complaining about the third round of her salsa dance, Eti Gordon "suddenly needed help in order to walk." The couple consulted a neurologist, and at first "They feared that she had cancer of the spinal column, but that was unfortunately not the case." This regret expressed by Gordon explains how a difficult and dangerous disease with a chance of a cure is preferable to what is in store for them in the immediate future.

"Obviously I fell into depression at first," Gordon remembers, "but then my wife looked at me and gave me a kick up the rear end, saying, 'You're an entrepreneur. Think of something to do. If there's no cure for ALS, find one. I thought that it would get me out of my depression and give me hope and strength to fight."

Towards the end of 2015, Eti already needed a wheelchair. In January 2016, the Gordons took a trip to New Zealand. With the wheelchair, they went on all the paths that could be traversed. They hired a helicopter to enable her to see the mountains and the landscape. After they got back from the trip, Eti lost her voice and ability to speak, and shortly afterwards her control over her hands. The next stage was difficulty in eating, which required a PEG feeding tube implant.

She lost her ability to breathe in early 2018 and needed a respirator. She communicates with her eyes: a camera coordinated with her eyelids enables her to move with a cursor on a screen and use it to write. Gordon went on a quest to find a way to relieve and improve her situation. He is totally involved in NeuroSense, and hopes that its drug passes Phase II and Phase III trials quickly and is put into use. He candidly says, however, "How much it will help my wife is another question. ALS kills nerves in the spinal column, and these do not regenerate. It's like a lottery: we don't know what died and what is still alive, and whether they will function again if the pressure is removed. What is dead is dead, and my wife is unfortunately at an advanced stage of the disease."

Ben-Noon objects at this point, and interjects, "Eti is far more optimistic. I visit her quite often. She has hope, and the hope of the patients you know keeps you moving forward." Gordon adds, "One of the things I did was to give her hope and joy of life. At my most difficult moments, I compare myself to Jakob the Liar (the main character in the Holocaust novel of that name by East German Jewish author Jurek Becker, who encourages his friends with fictitious optimistic reports about the imminent end of the war, S.L and G.W.). At other times, however, I hope that it is realistic, and that it will be possible to relieve her situation and restore the functions that she has lost."

"You need a lot of naivete and innocence"

As mentioned, Yossi Gross lives in Moshav Mazor with all of his siblings and his father, 98, a cofounder of the moshav. "He still drives and works in the field. He's alive and kicking. He sells securities on the stock exchange every day. He is also the oldest investor in NeuroSense, together with my son, Amir," Yossi Gross says. He has been in the medical devices sector for many years. He founded many companies, "some of which succeeded and some of which failed," he says. 18 months ago, he was involved in a huge exit with a company named Valtech Cardio, which developed the Cardioband System for transcatheter repair of the mitral and tricuspid valves. He founded the company with Amir, who managed the company. Valtech was sold to Edwards Lifesciences Corporation (NYSE: EW).

Gross's sister, Shoshi, also lives in Moshav Mazor. Everything changed when she went to his house to complain about slowing down on her weekly stroll. Her situation deteriorated very quickly after that complaint, and "I didn't understand what was happening," Yossi Gross remembers. "I thought maybe she had a tumor, because her abdomen was a little swollen. I sent her for a CT scan, I sent her to specialists, and no one saw anything. She had already begun limping. I took her to Tel Hashomer, where they did tests, and after an hour, the doctor came out and said, "She has ALS. There's no hope," just like that.

Shoshi died only six months later. Towards the end, she was hospitalized in Beit Rivka. Gross had to travel to JP Morgan on business, but he was afraid. "I asked the hospital department manager whether I should go. He told me, 'The show must go on.,' but when I landed, they called me to tell me to return, because she died. That's how it ended. It was two years ago on January 9."

"Globes": But it did not really end for you.

Yossi Gross: "That's right. I started thinking, 'What's going on here? A disease with no cure? That no one can do anything about?"

During the seven-day mourning period for his sister, he shared this thought with a good friend, former Teva business development manager Prof. Itzhak Krinsky. Krinsky told him that there was a startup he knew about, and asked if he wanted to meet the CEO. Gross and Ben-Noon met at a café. Since then, Gross has contributed to NeuroSense his money, and even more so his connections, his boldness, and what he calls the courage to develop.

Gross has ample boldness and courage. He studied electronic engineering and then aeronautical engineering at Technion. When he finished his studies, he said, "I'm not going to a regular job to punch a time clock; I'm a free spirit." Israel Aerospace Industries (IAI) was developing the Lavi fighter plane at the time, however, and actively recruited him. He worked at IAI for nine years and left in 1986, one year before the project was terminated.

Then a delegation from US medical device supplier Becton Dickinson & Co. visited Israel looking for technology for using electric pulses to administer drugs. "I knew nothing whatsoever about medical devices and had no understanding of drugs or electric pulses, but I said, 'I can develop this.'"

It sounds naïve to think that you could do something that you never tried before.

"You need a lot of naivete and innocence to do what we're doing. Most of the products that I began to develop were so complicated and long-term that without the naivete to believe and the courage to do it, we never would have started at all."

Gross founded Rainbow Medical nine years ago together with Efi Cohen-Arazi, and they managed to raise $300 million for it. "We focus mainly on therapeutic medical devices with markets of over $1 billion, and only for needs with no solution," he says, "not on all sorts of things that will be good to have, or which improve the quality of life. On our table are Alzheimer's Disease, blindness caused by macular degeneration, and life-threatening hypertension. Our field is one with big risks and large investments, because it takes $60-80 million to reach the market with such products, and development takes years, but this is the field on which we like to play."

"To slow down progress a lot"

Gordon began his career as one of the first employees at New Dimension Software, founded by Yossie Hollander and Roni Einav, which made products for managing large computer centers. When New Dimension was sold in 1999 for $650 million to US company BMC Software, one of the world's largest software companies, Gordon became BMC's CTO, and lived in Houston with his family.

In 2007, his daughter wanted to serve in the IDF. The family returned to Israel, and together with Yuval Cohen, Gordon founded Neebula Systems, a company in a similar field - cloud computing systems. He posted a good exit in 2014, when Neebula was sold to ServiceNow Inc. for $100 million. "The exit was a reasonable success," Gordon says dismissively, "but what is more important is our success within ServiceNow, a giant company with a market cap of over $30 billion, where I'm part of the innovation team."

ALS is classified as a rare disease. How rare? At any given moment, one out of every 10,000 people has ALS (700 people in Israel are currently diagnosed with the disease). On the other hand, the chances of contracting the disease are no different from the chances of getting multiple sclerosis, a disease of great interest to drug companies. Since the life expectancy of ALS sufferers is much shorter, however, (three years), there are far fewer patients at any given moment, which makes it a small market for the drug industry.

There are many cases in the drug industry in which a given ingredient has an effect on other things besides the medical problem for which it was tested. One of the most famous such cases is Viagra, which originated in a clinical trial to test an ingredient for treatment of hypertension. When the patients reported its welcome side effect, however, the company abandoned the drug for treatment of hypertension in favor of a market that was many times larger. There are many other such cases.

The drug companies therefore tend to test additional formulations of their active ingredients, but do this when large markets are involved. "When a disease with few patients is involved," Gordon says, "they are less interested in testing drugs, certainly new drugs, but also existing drugs."

Gordon knew that he had to act quickly. The drug he is looking for must contain one or more ingredients that have already been tested and found to be safe for use on human beings. "Looking for ingredients that were not tested on human beings was pointless," he explains, "because producing a drug from such ingredients takes 6-10 years and costs a huge amount of money."

Gordon's father worked in the experimental medicine department at Hadassah Medical Center. One of his colleagues recommended that he conduct a trial on zebrafish instead of on mice or other laboratory animals. He began trying out various ingredients on the fish, and also offered to test at his own expense the ingredients that other people were working on. One day, he noticed a small story in "Globes" about NeuroSense, and met Ben-Noon.

They eventually arrived at a combination of two ingredients, one of which was tested on patients many years ago in a trial by a large drug company, but which produced only a negligible change. The second ingredient helped a little. The combination of the two, however, gave a result, at least on fish, "that was about double the benefit from our previously most successful ingredient."

Gordon, Gross, and Ben-Noon show a series of pictures of fish whose nervous system is visible in their transparent bodies, and show what the nerve disorder of a sick fish looks like, how their swimming orbits lose direction, and how a sick fish that received the drug is in a better state - not like a healthy fish, but almost as good.

The dosages of the combination are now being made precise. NeuroSense, which has raised $1 million to date and is currently completing another financing round, hopes to begin a Phase II human trial in mid-2019. The company is negotiating to obtain a grant from US medical concerns interested in the trial. Incidentally, one of the members on NeuroSense's advisory board was the late triathlete and iron-man Shay Rishoni, who contracted ALS in 2011, after which he devoted himself to promoting and accelerating research into the disease. He also participated in races in order to increase awareness of the disease, surrounded by good friends running next to his wheelchair and pushing him. His last race was the 2018 Jerusalem marathon. He died in May 2018.

For Shay it is too late, but if development of the drug is successful, what can it do for other patients?

Gordon: "We hope that it can double the lifespan of patients. I don't think that it will be a complete cure."

Gross: "Since it's a disease that is detected in the early stages, our hope is that its progress can be greatly slowed, and maybe even stopped completely."

How Israel became of popular hub for development of ALS drugs

ALS is a fairly popular focus in the Israeli drug development sub-sector. Israeli ALS companies benefit from great academic expertise in both the central nervous system (nerve cells) and the immune system, which is probably one of the factors in generating or mediating the disease. Israel also has expertise in stem cells, and some of the companies were founded on that basis.

Israel also has a history of a strong lobby of ALS patients, including Felix Shlomovich, Avichai Kremer, Shay Rishoni, and others. They not only increased awareness of the disease, but also raised money for research through the Prize4Life association and for development of products supporting paralyzed patients.

Another reason why Israeli companies select ALS as a leading indication for development is that it is relatively easy to begin clinical trials for treatments of the disease. ALS patients have very little to lose.

The leading companies at present are Brainstorm Cell Therapeutics (Nasdaq: BCLI), which is already in an advanced trial using stem cells from the patients themselves; Kadimastem (TASE: KDST), which has begun a trial with fetal stem cells; ALS Mobile Analyzer, whose product for precise monitoring the progress of the disease and accumulating information likely to develop in future drug development was developed with help from Prize4Life; EyeControl, which developed a device for reading eye movements; and Immunity Pharma, which is developing a drug for ALS based on the immune system.

Published by Globes, Israel business news - en.globes.co.il - on March 25, 2019

© Copyright of Globes Publisher Itonut (1983) Ltd. 2019

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Yossi Gross and Ariel Gordon Photo: Inbal Marmari
Yossi Gross and Ariel Gordon Photo: Inbal Marmari
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