There’s a reason why mothers are instructed to breastfeed their babies soon after they’re born. The milk they produce in the days after giving birth is rich in nutrients, immune cells, and antibodies. While this “first milk,” also known as colostrum, is crucial in getting newborns off to a healthy start, PanTheryx CEO Mark Braman says the fluid’s components can also help resolve gastrointestinal disorders rooted in the gut microbiome. Now, the company has $50 million in new capital to ramp up its research.
The fresh cash comes from Perceptive Advisors, a firm that invests in life science companies. Boulder, CO-based PanTheryx has already commercialized a product developed to relieve diarrhea in children and adults. Braman says his company’s approach can also apply to clostridium difficile infection, a type of gut infection. Other GI diseases that the company is researching include two types of inflammatory bowel disease: Crohn’s disease and ulcerative colitis.
The PanTheryx expansion plans come as a growing number of biotech startups take aim at the gut microbiome, with some of them encountering setbacks. Much about the microbiome and its role in disease remains a mystery, but Braman, a former Pfizer (NYSE: PFE) executive, contends that nourishing gut bacteria is an untapped solution.
“The gut influences so many different diseases,” Braman says. “It only stands to reason that nutrition will play an important role in that.”
Founded in 2007, Braman says PanTheryx’s initial focus was acute infectious diarrhea, a type of diarrhea typically caused by viruses. The disease is common, and it kills an estimated 1.5 million to 2.5 million children worldwide each year. Studying the data, PanTheryx found that incidence of diarrhea was quite low in babies, particularly in the first six months of life. That research led the company’s scientists to colostrum. Obtaining colostrum from new mothers isn’t practical, so PanTheryx turned to bovine colostrum, the first milk produced by dairy cows.
PanTheryx’s anti-diarrhea product, called DiaResQ, is a powder meant to be mixed with water and then swallowed. In addition to colostrum, the product contain antibodies from chicken eggs. Braman says this combination addresses viral, bacterial, and parasitic causes of infectious diarrhea. The product was developed to pass through the stomach and into the small intestine where it binds to pathogens and flushes them out, Braman says. The components of the product also reduces inflammation and promotes repair of tissue in the gut.
Data from a clinical trial enrolling 325 children were mixed, however. According to results published last year in BMJ Global Health, the PanTheryx product was no better than a placebo at reducing the duration of diarrhea, the main goal of the study. But the stool of children who were given the PanTheryx product showed a “significant reduction” in pathogens that cause diarrhea. PanTheryx went ahead and launched DiaResQ last year, and the product is now available over-the-counter online and through retailers such as Walmart (NYSE: WMT), CVS Health (NYSE: CVS), and Walgreens.
Beating a placebo in a clinical trial is essential to support FDA approval of a drug. But the PanTheryx diarrhea product isn’t a drug. It’s a “food for special dietary use.” Products in this category address a particular dietary need and don’t require a prescription or a physician’s supervision. The slightly narrower “medical foods” category encompasses products intended for dietary management of a specific disease. Medical foods are intended to be taken under medical supervision.
Foods for special dietary use and medical foods face limitations on the claims that they can make, and those restrictions have gotten PanTheryx into hot water. In 2017, the FDA sent two warning letters to PanTheryx subsidiary APS Biogroup saying that therapeutic claims on labels characterized the products as drugs, which they were not. Braman says the products belonged to a PanTheryx customer. In addition to its own colostrum production, PanTheryx is also a contract manufacturer for companies that incorporate the fluid in products such as baby formula. He says the labeling language was changed to address FDA concerns.
Bovine colostrum is the backbone of PanTheryx’s product pipeline. The colostrum comes from 1.4 million cows at 1,000 US dairy farms, which freeze the first milk on site, Braman says. PanTheryx picks up the colostrum and trucks it to facilities in Phoenix and Ripon, CA, that PanTheryx acquired in 2017 to bolster its production capabilities. In addition to securing colostrum supply, Braman says his company also has patents on its production process, which involves pasteurizing the colostrum and drying it. But PanTheryx does not bioengineer the antibodies or proteins in the colostrum. Braman says the antibodies that end up in the product depend on the vaccines given to the animals.
“The cow and hen are the bioprocessor,” Braman says. “They’re very efficient at delivering antibodies and growth factors into the final product.”
As PanTheryx expands its research to specific GI disorders, it will need to produce more robust data that stands up to greater scrutiny. To date, PanTheryx’s research in c. diff infection and inflammatory bowel disease is preclinical. The company is also studying applications of its technology in addressing drug induced injuries, such as the gut damage caused by chemotherapy. Braman says clinical trials testing PanTheryx candidates in these applications could start by the end of this year.
Not all of the PanTheryx product candidates will be biologic drugs. Some might be medical foods, which offer a faster path to market because the FDA does not require them to go through the three phases of clinical trials required of drugs. That’s the pathway chosen by Whole Biome, a San Francisco company that plans to launch a type 2 diabetes medical food next year. Braman says that if all goes well, PanTheryx’s medical foods could reach the market in two years. The company’s biologic drugs could follow two to three years after that.
Earlier investors in PanTheryx include private equity firm Pegasus Capital Advisors. PanTheryx says it has raised $170 million total. The new $50 million in capital will be split between commercialization of DiaResQ and research and development of new product candidates. Depending on the progress of the research, Braman says those candidates could be developed in partnership with pharmaceutical companies or with large food or nutrition companies.
“We know the kinds of resources they can [bring to] bear, we don’t have to develop this all ourselves,” says Braman, a former vice president in Pfizer’s nutrition group. “We do believe it’s important to at least get the preclinical and Phase 1 work so you have sufficient data that would interest big players.”
Photo by Flickr user U.S. Department of Agriculture via a Creative Commons license
这就是为什么母亲在出生后不久就被要求母乳喂养孩子的原因。他们在出生后的日子里生产的牛奶富含营养物质、免疫细胞和抗体。尽管这种“第一牛奶”也被称为“初乳”，在帮助新生儿健康起步方面至关重要，但 PanTheryx 首席执行官马克•布拉曼( Mark Braman )表示，这种液体的成分还可以帮助解决根植于肠道微生物群中的肠胃疾病。现在，该公司有5000万美元的新资本来加强其研究。
新的资金来自 Perceptive Advisors ，一家投资生命科学公司的公司。总部位于 CO 的 Boulder 公司已经将一种用于缓解儿童和成人腹泻的产品商业化。Braman 说他的公司的方法也适用于艰难梭菌感染，一种肠道感染。公司正在研究的其他 GI 疾病包括两类炎症性肠病：克罗恩病和溃疡性结肠炎。
PanTheryx 的扩张计划出台之际，越来越多的生物科技初创企业瞄准了肠道微生物，其中一些企业遭遇了挫折。关于微生物及其在疾病中的作用仍然是个谜，但前辉瑞（Pfizer）公司（ NYSE ： PFE ）高管布拉曼认为，营养肠道细菌是一个尚未开发的解决方案。
“肠道影响着许多不同的疾病，” Braman 说。“这只是有理由认为，营养将在这方面发挥重要作用。”
Braman 说 PanTheryx 最初的重点是急性传染性腹泻，这种腹泻通常是由病毒引起的。这种疾病很常见，每年全世界估计有150万至250万儿童死亡。研究数据时， PanTheryx 发现婴儿腹泻的发生率很低，尤其是在生命的前六个月。这一研究导致该公司的科学家们进入了初创期。从新妈妈那里得到初乳是不实际的，所以 PanTheryx 转向了牛初乳，这是奶牛生产的第一批牛奶。
PanTheryx 的抗腹泻产品 DiaResQ 是一种粉末，可以与水混合，然后吞咽。除了初乳外，该产品还含有鸡蛋的抗体。Braman 说，这种结合可以解决传染性腹泻的病毒、细菌和寄生虫原因。Braman 说，这种产品被开发出来是为了通过胃和小肠，在那里它与病原体结合并将它们排出体外。该产品的成分也减少炎症和促进组织修复肠道。
然而，有325名儿童参加临床试验的数据是混合的。根据去年发表在 BMJ Global Health 上的研究结果， PanTheryx 产品在减少腹泻持续时间方面并不比安慰剂好，这是该研究的主要目标。但接受 PanTheryx 产品的儿童粪便显示，导致腹泻的病原体“显著减少”。PanTheryx 去年推出了 DiaResQ ，该产品现已通过沃尔玛（Walmart）（ NYSE ： WMT ）、 CVS Health （ NYSE ： CVS ）和 Walgreens 等零售商在线销售。
在临床试验中打败安慰剂对于支持 FDA 批准一种药物至关重要。但是 PanTheryx 腹泻产品不是药物。这是一种“特殊饮食用途的食物”。这类产品满足特定的饮食需求，不需要处方或医生的监督。稍窄的“医用食品”类别包括用于特定疾病饮食管理的产品。医用食品应接受医疗监督。
用于特殊膳食用途的食品和医用食品在声称它们可以生产时面临限制，这些限制已经使 PanTherx 进入热水。2017年， FDA 向 PanTherx 子公司 APS Biogroup 发出了两封警告信，称标签上的治疗声称将产品定性为药物，而不是药物。Braman 说产品属于 PanTheryx 的客户。除了自己的初乳生产， PanTheryx 也是一家合同制造商的公司，纳入液体产品，如婴儿配方奶粉。他说，标签语言被改变，以解决 FDA 的关切。
牛初乳是 PanTherx 产品管道的主干。Braman 说，这一初乳来自美国1000家奶牛场的140万头奶牛，这些农场冻结了第一批牛奶。PanTheryx 拿起柱状物，把它运到凤凰城和加州 Ripon 的工厂， PanTheryx 在2017年收购了这些工厂，以增强其生产能力。除了确保初乳的供应， Braman 说他的公司还拥有生产过程的专利，这涉及对初乳进行巴氏杀菌和干燥。但是 PanTheryx 并不能对初乳中的抗体或蛋白质进行生物工程。Braman 说，最终在产品中产生的抗体取决于给动物的疫苗。
“牛和母鸡是生物处理器，” Braman 说。“他们非常高效地将抗体和生长因子转化为最终产品。”
随着 PanTheryx 将其研究范围扩大到特定的 GI 疾病，它将需要产生更可靠的数据来经受更严格的审查。迄今为止， PanTheryx 在弥漫性感染和炎症性肠病方面的研究处于临床前阶段。该公司还在研究其技术在治疗药物引起的损伤，如化疗引起的肠道损伤方面的应用。Braman 说在这些应用中测试 PanTherx 候选药物的临床试验可能会在今年年底开始。
不是所有的 PanTheryx 产品候选者都是生物药物。有些可能是医用食品，这提供了一个更快的市场途径，因为 FDA 不要求他们通过三个阶段的临床试验所需的药物。这是旧金山公司 WholeBiome 选择的途径，该公司计划明年推出2型糖尿病医疗食品。Braman 说，如果一切顺利的话， PanTheryx 的医疗食品将在两年内进入市场。该公司的生物药物可能会在两到三年后上市。
早些时候， PanTheryx 的投资者包括私募股权公司 PegasusCapitalAdvisors 。PanTheryx 表示已经筹集了1.7亿美元。新的5000万美元的资本将在 DiaResQ 的商业化和新产品候选人的研发之间分配。布拉曼说，根据研究进展，这些候选人可以与制药公司或大型食品或营养公司合作开发。