Miracle of Regeneration in Placentas, a New Focus for Investment: Interview with Dr. Harrell, CEO of Regenerative Processing Plant, LLC

几周前的除夕时,Celularity,一家开发胎盘干细胞的公司获得了2500万美元的投资,干细胞治疗再次成为了投资热点。然而在上一次干细胞投资热潮中,人们发现这种神奇的细胞并不好驾驭。然而自2013年起,兰德尔·哈勒尔(Randall Harrell)博士和他的 Regenerative Processing Plant(下文简称PRR)公司采用了一种新的干细胞开发思路,成功将6款产品推向市场,即将完成同样是千万美元级别的B轮融资。

A few weeks ago, on Chinese New Year’s Eve, Celularity, a company which aims to develop placental products, has received a $250 million investment. Stem cell therapy has once again become a hot spot for investment. However, in the last boom of stem cell investment, people discovered that stem cells are not easy to manage. But since 2013, Dr. Randall Harrell and his company, Regenerative Processing Plant, LLC, have adopted a new idea for the development of stem cells and successfully introduced 6 products to the market. They have their A-Round financing and are now looking for B-Round financing.

兰德尔·哈勒尔博士
Dr. Randall Harrell

整形医学:一门严肃的基础科学
Plastic Surgery: A Serious Basic Science

哈勒尔博士是一位资深的整形医生,他毕业于德州贝勒医学院,曾在埃默里大学从事肿瘤免疫学研究,之后师从心血管手术之父Michael Debakey 研究再生医学——那时候甚至没有再生医学这个概念,至今已经四十年了。人们可能会好奇,为什么一个整形医生会对再生医学感兴趣?在大众的印象中,似乎整形医学就是整容术,就是制造“网红脸”。“很多人不知道,”哈勒尔博士说,“第一例移植手术就是由整形医生Joseph Murray完成的。他是移植手术之父,在1954年他成功实现了首次肾移植,因此荣获诺贝尔奖。”

Dr. Harrell is a seasoned plastic surgeon. He graduated from Baylor College of Medicine in Texas and studied tumor immunology at Emory University. He then studied with Dr. Michael Debakey, the father of cardiovascular surgery to work on regenerative medicine, when the concept of regenerative medicine had not been raised. He has been in this career for forty years. People may wonder why a plastic surgeon would be interested in regenerative medicine. In the public’s impression, it seems that plastic surgery is a cosmetic surgery intended to create a more aesthetically beautiful face.

“A lot of people don’t know,” said Dr. Harrell, “that the first organ transplant was done by a plastic surgeon, Dr. Joseph Murray. He was the father of transplant surgery. In 1954 he succeeded in achieving the first kidney transplant and was rewarded the Nobel Prize in 1990.”

整形医学最初的目的本是为战后的伤兵重塑五官。为了修补受伤的器官,产生了两种思路:一是利用其他的器官来修复损伤,这发展出了当今的移植学。另一种更加革命性的思路则是激发人的自我修复能力——如果人能像蜥蜴或蝾螈那样修复自身的损伤,又何须满世界找移植器官?由此衍生出了现在方兴未艾的再生医学,也是哈勒尔博士的追求所在:

The original purpose of plastic surgery was to reshape the facial features for the wounded soldiers after the war. In order to repair the injured organ, two ideas have emerged: One is to use donated organs to repair the injury, which has led to today’s transplantation. Yet another more revolutionary idea is to stimulate people’s ability to repair themselves. If people can repair their injuries like lizards or newt, why should they look for organs desperately all around the world? This idea is the foundation of the emerging regenerative medicine, which is Dr. Harrell’s pursuit.

“寻找一种让机体自我修复的方法,而非对机体大动干戈”
哈勒尔博士相信,在未来“向人体注射药物促进干细胞自我修复,将会比整形手术更加简单”。

“We can regenerate the body instead of doing surgery.”
Dr. Harrell believes that “In the future it would be a lot easier to inject medicine instead of doing surgery. We are going to inject things to stimulate people’s stem cells.”

1989年,哈勒尔博士在佛罗里达州成立了自己的整形诊所“青春之泉”,一边进行传统整形手术(迄今一共服务超过5万位患者),一边开发产品。2013时,哈勒尔博士发现“我已经有了太多的专利,”于是决定成立Regenerative Processing Plant,“为了人类的福祉,发展这些专利。”目前与RPP公司直接相关的专利共18项,哈勒尔还有更多的专利择机而用。

In 1989, Dr. Harrell established his own “Fountain of Youth” clinic in the state of Florida, where he performed traditional plastic surgery (having served 50,000 patients so far) while developing regenerative medicine products. In 2013, Dr. Harrell found that “I’ve got many patents”. So he decided to establish the Regenerative Processing Plant, LLC, and began to develop patents and products for the welfare of human being. Currently, there are 18 patents related with Regenerative Processing Plant while he has more patent for reserve.

在谈到这么多专利,他对哪个最自豪时,他说:“最重要的是今年2月刚获得的专利,这个法律地位牢固的专利是发展其他专利的基础。”哈勒尔博士一边运营自己的诊所,一边不断开发专利,现在又要经营公司,但他说:“只要有激情就不会觉得是‘工作’。”哈勒尔博士有时候早上4点就起来工作,40年来每周工作超过80小时,他对整形医学与再生科学的热爱激励他不断取得突破性进展。

此外,哈勒尔博士2001年时还曾参加过Medical Mission International组织的对中美洲国家萨尔瓦多的医疗救助,这项壮举曾获得诺贝尔和平奖的提名。

Of all those patents, which one is the proudest one for Dr. Harrell? He said, “The most valuable one is the patent which we just got issued in February this year. It gives us a strong patent position and will be the basis for the development of other patents.” Dr. Harrell runs his own clinic, while continuing to develop patents, and now he needs to run the company. But he said, “If you have a passion, you don’t think it is work.’”Dr. Harrell sometimes gets up at 4 AM and works 80 hours a week. His passion for orthopedics and regenerative science inspire him to make continual breakthroughs.

In addition, Dr. Harrell also participated in the medical assistance organized by Medical Mission International to El Salvador in 2001. This feat was nominated for the Nobel Peace Prize.

哈勒尔博士与肯塔基州州长马特·贝文,获CBS报道
Dr. Harrell with KY Gov. Matt Bevin, reported by CBS

源自胎盘的生物制品

Placenta Based Biomaterials

RPP公司已经成立5年了,他们一共有6款在销产品,都是从胎盘中提取的各种蛋白。RPP公司的胎盘由第三方NGO组织从产妇那里募捐而得,所以RPP公司的生物材料供应很充足。

Regenerative Processing Plant, LLC has been founded for 5 years. They have 6 products on market now, which are proteins and cytokines bioengineered from placentas. Their placentas are donated by a third party non-profit organization and the supply is sufficient.

胎盘中含有大量珍贵的干细胞,有些产妇会将胎盘冻存,为孩子留下一份珍贵的医疗储备,哈勒尔博士形容这些胎盘就是“金矿”。RPP公司开采出的“黄金”并不是某种成分明确的蛋白,而是多种细胞生长与调控因子的混合物,颇有些玄学的意味。但做过细胞培养的朋友都知道,培养基中总需要一点成分不明的“血清”,而且这些血清现在还无法被人工合成。科学家们也从中发现了一些重要的分子,比如近年引发学界热议,可能是“年轻分子”的GDF11。

There are many valuable stem cells in the placenta. Therefore some mothers will save them as a medical gift for next generation. Dr. Harrell would describe those placentas as “gold mine”. The “gold” mined by Regenerative Processing Plant, LLC has 770 cytokines, chemokines and growth factors instead of one single protein. Researcher who have done cell culture will know that a little ‘serum’ of unknown composition is always necessary for the medium, and those serum can’t be synthesized artificially yet. Scientists have also discovered some important molecules, such as the GDF11, known as “Youth Molecule”, which has drawn a lot of attention recently.

哈勒尔博士开发的药物比较接近丙种球蛋白这些血液制品,在FDA有特殊的管理办法。FDA将人体细胞、组织及其相关产物(HCT/P)分为多个种类,如脐带血这样直接来源于人体、主要用于移植的组织和细胞纳入联邦管理法规中第12章以及公共卫生法案第361节的管理(21 CFR 1271, PHS 361),只要证明产品的安全性(不含传染病)即可,不需要进行漫长而昂贵的临床试验。而更广为人知的克隆细胞、免疫细胞、基因疗法等特殊细胞属于PHS 351管理,需要进行临床试验才能向FDA申请上市许可。

Inside of chemical compounds or engineered proteins, Dr. Harrell’s products are closer to blood products such as gamma globulin. FDA classifies human cells, tissues, and cellular and tissue-based products (HCT/P’s) into multiple categories. Products such as umbilical cord blood (which is derived from human body directly, containing tissues and cells that are used primarily for transplantation) are subject to the regulatory of part 1271 of Code of Federal Regulations Title 21 and the Section 361 of Public Health Act, which only require proofs of safety(without infectious diseases) instead of long and expensive clinical trials.Some widely known special cell products such as clone cell, CAR-T cell, and gene therapy are subject to the regulatory of Section 351 of PHS, which requires clinic trails before a company can apply for marketing approval from the FDA.

(我国《药品注册管理办法》中对这类产品的部分规定:注册分类5中的人血液制品,如使用剂量不超过生理允许剂量范围,且未进行特殊工艺的处理,未使用特殊溶剂,在提出相关资料或证明后,可免报安全性研究资料。)

(“Regulations for the Administration and Registration of Medicines” in China stipulates that blood products fall in Category 5 can be waived for safety data after submitting relevant materials or certificates if the dose of the product do not exceed the physiologically tolerated range and if the product has not been treated by special processes including special solvents.)

RPP的8款产品

8 Products of Regenerative Processing Plant, LLC (6 are available in US)

这些人源的细胞生长因子一般不具有免疫原性,不会导致免疫反应,因此RPP产品的七万例使用中,没有出现一次需要向FDA报告的副作用。而这些蛋白就像细胞培养基中的血清,具有神奇的促进组织再生效果。

These human-derived cell growth factors are generally not immunogenic and do not cause an immune response. Therefore although there are over 70,000 treatments that have been administered, there are no side effects which need to be reported to FDA. These proteins are like serum in cell culture medium, which has a magical effect of promoting tissue regeneration.

使用RPP公司产品的患者中,有靠雾化疗法就避免了需要20万美元来进行肺移植的老太太;有通过在膝盖注射药物就避免了需要5万美元的膝盖移植的超重患者;还有仅使用眼药水就避免了视角膜移植的患者……虽然这些都是个案,但哈勒尔博士也清楚扎实科学证据的重要性,尽管FDA并不要求他们提供药效资料,但RPP将在B轮融资之后尽快展开临床试验。

Among patients who have used the company’s products was a woman who benefited from atomization therapy to avoid a lung transplant which would have cost $200,000. She was barely able to walk, but now is walking with no shortness of breath. There was an overweight patient who would needed a $50,000 knee transplant. However, after using Dr. Harrell’s injectable product, he grew new cartilage and now is able to exercise. Many patients are using the eyedrops alone to avoid periocular grafts. Although these are all excellent cases, Dr. Harrell also understands the importance of solid scientific evidence. Regenerative Processing Plant will start clinical trials as soon as possible after the B-round of financing.

哈勒尔博士与经PurAgen®(RPP公司产品之一)治疗康复的患者
Dr. Harrell with recovered patient who benefit from PurAgen®

RPP公司的产品来源于胎盘,而核心技术则来自哈勒尔博士开发的“D-MAPPS”细胞信号转导技术平台,这是一种综合病理模型平台。这个平台也是RPP与其他传统干细胞治疗公司的关键差异所在。哈勒尔博士认为:

“基于对细胞信号转导机制的了解,可以用一些蛋白质去刺激人体自身的干细胞,而非利用他人的干细胞,由此避免干细胞可能带来的免疫与感染等问题。”

此外,哈勒尔博士独特的冷冻消毒方法也是RPP公司的亮点之一。胎盘在中医中被称为“紫河车”,但是如果经过了高温处理,其中的活性成分便也损失殆尽。而哈勒尔博士的冷冻消毒法避免了高温、化学试剂或者射线消毒对蛋白质的破坏。有趣的是,这种特殊的消毒方法主要靠商业机密形式保护,而且是经过FDA技术认证的商业机密。

The products of Regenerative Processing Plant, LLC are derived from placentas while the core technology comes from the “D-MAPPS” cell signal transduction technology platform developed by Dr. Harrell, a comprehensive pathology model platform. This platform is also the key difference between Regenerative Processing Plant and traditional stem cell companies. Dr. Harrell believes:

“We work on how cells communicate with each other……We can bypass a lot of problems people has with stem cell (like immune response or infection) and stimulate your own stem cells to get the effect we want not by using somebody else’s stem.”

In addition, Dr. Harrell’s unique sterilization method is also one of the highlights of the company. If biomaterials are sterilized by high temperature, the active ingredients would be lost or die. Dr. Harrell has developed a cryo-sterilization method to avoid damage caused by traditional sterilization like high temperature, chemical reagents or radiation sterilization. Interestingly, this sterilization method is largely protected by trade secrets and it is a FDA-certified trade secret.

RPP已经具有稳健的资金流/h3>

Regenerative Processing Plant, LLC has a steady flow of money already

与许多疯狂烧钱的生物制药创业公司不同,哈勒尔博士的RPP公司成立已有5年,有8款在销产品,由500位合作医生开出了7万次处方,有稳健的收入。虽然RPP作为私有公司,不需要公开财报,但哈勒尔博士以他们缓解干眼症的Regener-Eyes介绍了公司的营收前景:

Unlike many money-burning biotech start-ups, Dr. Harrell’s company has been established for 5 years. 6 products have been prescribed by 500 doctors for 70,000 treatments, which produce a steady income. Although Regenerative Processing Plant is a private company and is not required for public disclosure, Dr. Harrell has demonstrated the company’s revenue prospect with Regener-Eyes®, an eye drops for dry eye syndrome.

干眼症是一种由于泪液质量异常引起的眼表面损伤,仅美国就有3000万人受其困扰。干眼症较难治愈,一般需要长期药物控制。国内一般以人工泪液控制为主,著名眼科药物公司艾尔建的特效药环孢霉素滴眼液(Restasis)去年销售额高达15亿美元。

Dry eye is a syndrome of ocular surface damage caused by abnormal tear quality, affecting 30 million people in the United States alone. Dry eye is difficult to cure and generally requires long-term drug control. In China, artificial tears are the mainstay while the sales of cyclosporine eye drops (Restasis®), manufactured by Allergan, has reached $1.5 billion last year.

RPP公司的Regener-Eyes对干眼症有非常好的缓解效果,甚至对部分经Restasis治疗无效的患者也依然有缓解作用。一瓶Regener-Eyes大概可供患者使用30天,每瓶售价150-190美元(同样剂量的Restasis每瓶售价接近400美元)。由于干眼症需要长期用药控制,如果患者认为有效,将会长期购买。RPP已和全美最大的眼科保健品连锁供应商Vision Source合作,正在培训医生,即将大面积推广Regener-Eyes。

Regener-Eyes® has a very good palliative effect on dry eyes, and even some patients who are resistant to Restasis® respond favorably to Regener-Eyes®. A bottle of Regener-Eyes® is available to patients at a price of $156-195 per bottle and could be used for a month. The same does of Restasis® costs nearly $400 per bottle. Since dry eyes require long-term drug control, patients will become long-term customers once they find it is effective. Regenerative Processing Plant, LLC has partnered with Vision Source, the largest supplier of eye care products in the United States, and is training doctors to promote Regener-Eyes® on a large scale.

经Regener-Eyes治疗康复的干眼病患者,她的故事可见: http://mydryeyes.org/testimonials.html
Patient who recovered thanks to Regener-Eyes®. Hear her testimonials at http://mydryeyes.org/testimonials.html

RPP的产品尚未纳入医保,但RPP会帮助暂时无法支付的患者以各种贷款方式购买。目前美国医保因党派变更较难纳入新品种,但医保是哈勒尔博士未来几年的目标。

Products of Regenerative Processing Plant have not been covered by Medicare yet, but the company has credit options for patients who are temporarily unable to pay. At present, it is difficult to get the US Medicare system to agree to cover new procedures, medications or biopharmaceuticals. However, Medicare approval is Dr. Harrell’s future goal.

除了面向一般消费者,RPP还和美国国防部签署了采购合约,提供4款特殊产品。可以说使用RPP的产品便是体验了美国大兵的治疗水平。

In addition to targeting general consumers, Regenerative Processing Plant has also signed Distribution and Pricing Agreement with the US Department of Defense to provide four special products. It can be said that using Regenerative Processing Plant’s products is supporting the treatment for American soldiers.

RPP即将完成B轮1000万美元融资,已在中国准备申报新药

Regenerative Processing Plant, LLC is looking to complete Round B financing of USD $10 Million and has prepared to declare new products in China.

RPP的融资已到B轮。哈勒尔博士计划在4月前完成 500-1000万美元的融资,目前一家“比苹果还大的企业”对RPP非常感兴趣,已经计划投资500万,基本实现融资目标,这笔资金将用于扩大产能。

The financing of Regenerative Processing Plant, LLC has reached the B Round. Dr. Harrell plans to complete a financing of $5 million to $10 million by April. This funding will be used to expand production capacity. Currently a partner who “is larger than Apple” has expressed interest in investing $5 million.

哈勒尔博士依然欢迎更多投资,尤其希望与中国投资者合作。RPP公司的科学顾问委员会中有多位华人教授。哈勒尔博士本人也与中国渊源颇深,都是“非常、非常好的回忆”。一位卢姓博士曾是哈勒尔的重要合作伙伴,他们曾在北京的5家医院试验一种除皱纹产品,最终得到了CFDA的初步批准。不幸的是,卢博士赫然离世,这个项目也被迫中断了,哈勒尔博士目前准备重新申请,完成老朋友的夙愿。

Dr. Harrell still welcomes more investment, and especially hopes to cooperate with Chinese investors. There are many Chinese professors on the Regenerative Processing Plant’s Advisory Committee. Dr. Harrell himself has an excellent relationship with China and Chinese physicians. One of Dr. Harrell’s former partners was Dr. Lu. Together they tested a wrinkle-removing product in 5 hospitals in Beijing and eventually obtained preliminary approval from the CFDA. Unfortunately, Dr. Lu passed away and the project was forced to be interrupted. Dr. Harrell is currently preparing to reapply and complete the long-cherished wish of his old friend.

除了RPP公司之外,哈勒尔博士也有一些专利可以按传统新药研发路线开发。随着Celularity成功融资,哈勒尔博士相信越来越多的人会开始关注胎盘制品。
最后,哈勒尔博士表示“干细胞与再生医学领域已经有很多玩家了,但是RPP拥有独特的专利。RPP不做干细胞,而是专注激发人体自身的干细胞,以治愈众多慢性疾病。RPP将会与伙伴们一起探索未来,成为比苹果还大的公司!”

In addition to Regenerative Processing Plant, LLC products, Dr. Harrell also has many patents that can be developed as traditional R&D route. With the successful financing of Celularity, Dr. Harrell believes that more and more people will begin to pay attention to placental products.

Finally, Dr. Harrell said “A lot of people know about stem cells and regenerative medicine…… There are a lot of things we have patented and we could do without stem cells. We work on stem-cell stimulators and we will affect a lot chronic diseases by stimulating people’s own stem cells. We have the right strategic partners and we could do lot of things and we could be bigger than Apple in the future!”

欲获得更多有关哈勒尔博士与投资Regenerative Processing Plant的信息,请联系projects@mybiogate.com

For more information about Dr. Harrell and investment in Regenerative Processing Plant, LLC, please contact projects@mybiogate.com

By RPP: The miracle of reproduction in the placenta

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