frequently asked questions

    What is "Fibrinogen-coated Albumin Spheres (FAS)"?

  • Fibrinogen-coated albumin spheres are very small and biocompatible spheres made from human albumin molecules, coated with a protein called fibrinogen. Both albumin and fibrinogen are natural molecules purified from healthy donors. We purchase the sterile, medical grade solutions as starting material and then transform the dissolved molecules into ultra-small spheres (median diameter of less than 0.5 micron). The spheres are so small that they will not obstruct even the smallest blood vessels (with typical diameter of about 5 micron). The spheres will be produced in a suspension that can be infused as a medical treatment into patients who can benefit from the treatment.

    What diseases can FAS treat?

  • FAS can treat several major types of diseases. For example, it can stop bleeding in patients with low platelet counts, platelets are cells in the blood responsible for the control of internal bleeding. We have administered the product to over 600 cancer and hematological patients in China who have low platelet counts. The treatment showed no side effects and improved their clotting time and bleeding condition. For patients going to surgery where there is a large blood loss expected, FAS can be administered prior to surgery to significantly lower blood loss. In an animal model where a soft tissue like the liver is injured (where the bleeding cannot be stopped by putting in a suture because the organ is so soft) administration of FAS reduces blood loss by about 55% compared to the control group. In addition to the ability to stop bleeding, FAS has a second function, it can mobilize stem cells from the bone marrow so that they can move through the blood toward a wound site to heal the wound rapidly. The wound can be a soft tissue, like the skin (please see "radiation-induced skin injury") or a hard tissue like a bone. In an animal model where a major bone fracture was induced, the fractures in the treated group heal significantly faster than the control group. The company is applying for a NIH grant to further confirm this finding, which will benefit a large number of older patients who will suffer from hip fractures

    Why are stem cells important?

  • Stem cells are very important cells in our body, they repair wounds and replace old tissues. For example, many people are aware that our liver can regenerate itself when a small piece is removed, such as during a live-donor liver transplant. The old theory said that the liver cells along the wound "know" that the other side is missing and so they divide to form a new lobe of liver cells. That old theory is wrong, because the liver cells that have not been removed are already mature liver cells, they cannot go back to a juvenile state to divide into a new liver lobe. What is happening is that stem cells in the blood go to the wound site, and when the signals there inform them that they are at a liver site, the stem cells transform (technically called "differentiate") into liver cells. We know this because of a famous trauma case: the patient had his liver so badly damaged that doctors need to infuse stem cells collected from a female volunteer. After the liver has healed, a biopsy of the new lobe reveals the cells are derived from the donor and not the patient's own cells. Fibroplate has obtained evidence that FAS can mobilize stem cells from the patient's bone marrow and promote accelerated healing of deep wounds which would otherwise not heal. Please see "radiation-induced skin injury."

    What is Radiation-induced Skin Injury (RSI)?

  • It is estimated that about half of all cancer patients will need radiation therapy (RT). That means about 800,000 patients every year in the USA will receive RT, among whom 95% will have some degree of skin injury from the radiation. The radiation oncologist will try to give the lowest dose of radiation needed (and in divided doses) in order to avoid Radiation-induced Skin Injury (RSI). But it is difficult to avoid, partially because of the weakened state of the patients. Also, a skin lesion may appear many weeks or even months after the RT so the patient may not even relate the "skin problem" with the irradiation event. Even if the patient returns to the radiation oncologist for treatment, currently there is no effective treatment for severe cases. Another kind of RSI occurs when an industrial nuclear accident occurs, such as Chernobyl or the Fukushima Daiichi nuclear incident in 2011. These are rare events but a large number of patients will need to be treated when it happens, precisely when the health support system nearby is most stressed and perhaps non-functional. Fibroplate has recently received an NIH grant which provides funding to confirm that FAS can effectively treat RSI, perhaps the only medication that can be used both immediately after the irradiation event as well as a long time after irradiation -- after the skin lesion appears. Fibroplate has also applied for an NIH grant that will fund studies in high dose exposures to show that FAS is equally effective in those situations.

    How does one know if someone has developed RSI?

  • The challenge with RSI is that the skin lesion typically becomes obvious only weeks (if not months) after the irradiation event. The primary physician or the dermatologist who examines the skin may not associate the skin lesion with irradiation. Even if they do, there is currently no effective treatment for the severe cases. There are four stages of RSI, all of which will catch the attention of the patient. (1) The mildest form is like a severe sunburn. (2) the next stage is the formation of dry blisters. (3) The third stage is the development of wet blisters, with increased likelihood of infections. (4) The worst cases become skin ulcers where the underlying tissues (muscles, fats, nerves, blood vessels) all die, leaving behind a large patch of exposed and unprotected tissues. Since RSI is a result of the therapeutic radiation dose, the medical profession is very motivated to have a cure for the problem. The patient will definitely go see a doctor. Even for patients who do not know that they have been exposed during an industrial accident, they will go seek help when the their skin symptoms appear. FAS is a ready-to-use suspension designed to be administered to a large number of patients even in the absence of sophisticated medical support systems. It can be injected directly into a vein when an intravenous fluid line has not been or cannot be established. This is because FAS are not cells and will not break when pressure is applied. FAS does not require any blood work to be done first, and it can be used on patients of all blood types (no need for type-and-cross). It works immediately after intravenous administration. It has a shelf life of at least 2 years at room temperature and requires no specialized equipment for maintenance.

    What are the current methods of treatment for RSI?

  • The mildest forms of RSI (please see "symptoms of RSI") will be self-healing. Unfortunately, nobody knows how severe it may be. Typically, the patient will receive some cream to apply locally to the skin but they do not work if the lesion progresses to the next stage. At some point, the doctor will recommend plastic surgery. Typically, the plastic surgeon will try to transfer a large "tissue flap" from a "healthy area" of the patient to cover the wound. A "flap" will mean the whole piece containing skin, fat, muscle and connecting blood vessels will have to be transferred. It is very expensive and often the flap does not take due to the weakened state of the patient. Then the patient will have two wounds: one created by the radiation oncologist and a second one by the plastic surgeon.

    What is Fibrinoplate-S (FPS)?

  • FPS is the name of our Drug Product. The "S" following Fibrinoplate indicates that the formulation is a suspension that is ready-to-use. The bottle contains 100 mL of the suspension. The effective dose in most cases is only 1 mL per kilogram of the weight of the patient. This means one bottle of the product can stop the bleeding of a 100 kg (220 lb) person. In some situations, it may be advantageous to freeze-dry FPS to reduce the weight of the product, e.g. in use for space exploration, to save the life of the astronauts after their exposure to cosmic rays. But for earth-bound uses, there is no good reason to freeze-dry the suspension because the dry powder would then need to be reconstituted before it can be used, taking up precious time and injection equipment.

    What is the goal of Fibroplate, Inc.?

  • The immediate goal of the company is to ask the FDA (Food and Drug Administration) for permission to start the human trial Phase I. This we will do by submission of an IND (Investigative New Drug) detailing how the Drug Substance and the Drug Product are made and how the patients will be treated. The purpose is to prove the safety of the product. We have hired a clinical research organization (CRO) called Kinexum Services LLC (Harpers Ferry, West Virginia) to conduct this clinical trial. Alternatively, the company may use the services of Boston Biomedical Associates (BBA.) Fibroplate, Inc. does not need to hire additional personnel to do this work. The clinical lots of the product have already been produced and stored at the Las Vegas cGMP facility. In parallel, the company will conduct experiments in Chicago under the supervision of Dr. Amelia Bartholomew at the University of Illinois in Chicago. The work will start as soon as funding is available from an NIH SBIR grant (Phase II). The data will satisfy the Animal Rule (please see "Animal Rule"), which will move us closer to selling the product to the US government under the Strategic National Stockpile program. The next step is to show that FAS is effective in accelerating the healing of bone fractures in old rats that are prone to osteoporosis. Fibroplate has data showing the efficacy of FAS in young rats with fractures. The company has applied for another NIH grant that should fund this project beginning first quarter of 2020. This will allow us to go after the orthopedic market where there are about 1.5 million surgeries done in hip or knee replacement in the USA every year. Accelerated healing will allow patients to move around sooner, decreasing the chance of potentially fatal blood clot formation.

    Why is Fibroplate, Inc. incorporated in Nevada?

  • Nevada is a state without Corporate Income Tax and no personal income tax. Las Vegas welcomes high tech companies even though it is not well known for that kind of industry. The labor cost is very reasonable and many highly educated Californians are willing to fly or drive to Las Vegas to work Monday to Friday and then return home for the weekend.

    What is the inspiration that caused the invention of Fibrinogen-coated Albumin Spheres?

  • The inspiration that caused Dr. Yen to invent this product comes from the observation that platelets become sticky only after their activation in the blood. And the major biochemical event in the activation step is the binding of a protein called fibrinogen onto the surface of the platelet. Since Dr. Yen has already invented the precise method of making very small albumin spheres, the thought was "What if one can coat the albumin spheres with fibrinogen molecules, will the product be effective in augmenting the body's capacity to stop bleeding?" The answer is: Yes. Several animal models have been tested, including rabbit, mouse, rat, and dog. In animals treated with radiation and anti-platelet antibody (to reduce their platelet count to dangerously low levels), FAS has been shown repeatedly to lower bleeding time and bleeding volume. In one experiment, the effect of FAS was compared to that of a transfusion with platelets: the effect of FAS lasted longer and showed no side effects. FAS has been administered to human volunteers in China. These are patients with cancer or hematological problems that make them bleed easily. Some of them were actively bleeding. But the administration of one dose of FAS allowed them to stop bleeding with no observed side effects. A further benefit from the administration of FAS is that this product can also mobilize stem cells. Therefore, the product will benefit patients who are in need of faster tissue regeneration, such as patients with major spinal injury or neurological diseases.

    How effective is your product in treatment of high dose radiation exposure?

  • Duke University is one of the few institutions in the USA equipped to handle animals after high doses of radiation. The NIH has granted a contract worth over $4 million so that a team of 25 PhD and MD experts in the field can collect data on whether FAS can improve survival in mice after exposure to lethal doses of radiation. The team used a high dose of radiation so that 95% of the mice will die, leaving a survival rate of 5%. While the control group has only a survival rate of 5%, the treatment group receiving FAS shows a survival rate of 60% -- a 1200% improvement over the baseline. This remarkable result has already been published: Article: Fibrinogen-Coated Nanospheres Prevent Thrombocytopenia-Related Bleeding Authors: Anthony D. Sung, Richard Yen, Divino Deoliveira, ... Journal: Biology of Blood and Marrow Transplantation 02/2015; 21(2):S111-S113

    What recognitions and awards have Fibrinogen-coated Albumin Spheres received?

  • As far back as 2009, the North Koreans were threatening to shoot missiles at Hawaii. Dr. Yen wrote a letter to the Secretary of Defense at that time, Dr. Robert Gates, informing him that Fibroplate has a product that may save lives after a nuclear event. He invited Dr. Yen to talk to a special committee in Washington on August 31, 2009. The committee suggested data collection on whether FAS can improve survival of patients after exposure to lethal doses of radiation. NIH awarded a contract worth $4 million+ so that a team of 25 PhDs and MDs at Duke University (North Carolina) can independently confirm the finding that FAS can improve survival of mice from 5% (in the control group) to 60% after treatment with FAS. Duke University was chosen because they have the animal facility and world-class brain power to study every facet of the physiology of lethal radiation. Our company is recognized as the producer of the product in the published article: Biology of Blood and Marrow Transplantation 02/2015; 21(2):S111-S113. Earlier studies have shown that FAS is very effective as a prophylactic agent, which means it works when given before the radiation exposure (which may not be practical). Further studies show that FAS is even more effective when given soon after exposure to radiation (which is called "mitigation") but before the skin lesion becomes visible. However, it is more practical to administer FAS only when the skin lesions show up (typically weeks or months after the irradiation event). NIH awarded a SBIR grant to Fibroplate, Inc. in December 2018. With that the company has definitively proven that FAS is an effective therapeutic agent for radiation-induced skin injury, and the mechanism is the mobilization of stem cells to the deep wound to produce effective healing. The National Aeronautics and Space Administration (NASA) also awarded Dr. Yen twice for producing a countermeasure that can potentially save the lives of astronauts on their long journey to Mars. The first award-winning white paper was titled "Countermeasure for radiation damage in space" (2016) and the second was titled "Tissue Regeneration After Radiological and Acute Trauma in Space" (2017).

    What competitors are expected to use FAS for the treatment of RSI?

  • First, there are basically no competitors worldwide for a product like fibrinogen coated albumin spheres because the technology of making nanometer-sized biocompatible spheres itself is very challenging. Most imitators try to compete by using material (e.g. plastic polymers) which are often not compatible with the body, the body will remove those unnatural particles within minutes. Sometimes direct harm to the body can be observed, as explained below. Others try to grow platelets outside the body, even though platelets are cells with very short shelf-life. Two groups tried to enter the platelet arena by growing platelets in culture "tanks". They both originate from Boston Children's Hospital. The first team was led by Dr. Thorsten Schlaeger, who identified two chemicals to increase the production of platelets from pre-platelet cells. The other team was led by Dr. Joseph Italiano, who focused on the mechanics of platelet formation. However, regardless of how well they may succeed in the future, their product is a platelet, which will have the same disadvantages of donor platelets: having shelf-life of 5 days and causing antibody formation in the recipient, not to mention the high cost of purifying the harvest platelet from chemicals in the culture broth. A group in Santa Barbara took another approach. Mr. Nishit Doshi, a researcher from the Department of Chemical Engineering, first produced a hard core of plastic material, coated it with proteins and then dissolved the plastic material so that the synthetic particle can be flexible enough to function as a synthetic platelet. There is apparently no update on how well this product works in animals with low platelet count and whether it is safe for intravenous administration. Second, in terms of using a similar product (which so far we have not seen in the market or in literature searches conducted by various Patent Offices worldwide) for the treatment of RSI, the chance of this happening is minimal. This is because scientists working on a "platelet-like" product (such as the two groups mentioned above) will be focusing on hemostasis (stopping bleeding). They will not be able to create a platelet-like product that can cure RSI. The healing of a deep wound like RSI would require the mobilization of stem cells, which is not likely to happen with competitors trying to achieve hemostasis with plastic polymers. The healing of a deep wound such as RSI would require the coordinated recovery of many tissues, e.g. the muscles, the nerves, the underlying blood vessels, the skin, the fat cells and connective tissues. Platelets and platelet-like substances cannot promote the simultaneous healing of such a wide range of different cells and tissues. However, FAS has a second mechanism of action, which is the mobilization of stem cells from the bone marrow of the patient, which nobody can achieve using other products. Therefore, we expect nobody to be able to compete with this project of using FAS for the "therapeutic treatment of RSI."

    What s cGMP?

  • Good Manufacturing Practices (cGMP) means the product is made with an FDA compliant Quality System that can essentially guarantee that every bottle of product has the same degree of safety and effectiveness. The "c" before the GMP means "current" which means the company is using the latest (current) and the best technology possible.

    What is the state of development for the FAS product?

  • In the life cycle of developing a drug, nobody expects perfection with the "first generation" product. A lot of work has to be done to improve the composition of the "drug entity" and then the method of mass production. A separate manufacturing company, called Fibrinoplate, Inc. (FI) has been established by Dr. Yen solely for the purpose of mass-production of FAS. It has already completed those steps for this product. This company Fibroplate, Inc. (FB) will commission FI to manufacture the product in the cGMP facility. Just like many pharmaceutical start-up companies that will contract with an outside CMO (contract manufacturing organization) to make its product, FB have executed an agreement with FI where FI will make the product. This will save FB investors' resources in that FB will not have to purchase a duplicate set of equipment to make a product, that FI already owns. In fact, for the clinical lot of FAS, FI has been produced, bottled and is ready to transfer these bottles to FB for use in human clinical trials. However, as Sponsor of the clinical trials, FB will still need to do some quality control tests on these bottles before FB can use them on patients during the clinical trials. Previous batches have shown that the product is stable for at least 2 years during storage at room temperature without the need of specialized equipment for storage.

    What market resistance do you expect?

  • We do not expect any market resistance to our entry into the platelet replacement arena. In the area of radiation-induced skin injury our product will be very welcome because at the present time there is no other effective treatment.

    How will FDA regulate Fibrinogen-coated Albumin Spheres?

  • In a letter (Request for Designation) to the FDA in 2011, Dr. Yen has outlined the characteristics of the product, its method of production and some of the medical benefits. FDA agreed that the product "fibrinogen coated albumin spheres" would be regulated by the Center for Biologics Evaluation and Research (CBER) as a biological product. Being a biological product has many advantages: (a) unlike a "drug molecule" which will be regulated by the Center for Drug Evaluation and Research (CDER), our product will be regulated by CBER instead of CDER, which has very different rules, (b) a biological product is defined not be a single chemical structure but is defined by the quality of the raw material and "precise method of production" which will make it almost impossible to copy; (c ) because of the complexity of the product, even after the patent expires (20 years after the date of filing), all potential competitors will have to repeat the clinical trials: there is no "generic" competition; (d) by that time, we will have dominance over the market, and any competitor will have to show in clinical trials that their product is substantially better than our product, which will be very hard to accomplish. It will be more cost effective if they go to a different arena to recover the cost of clinical development for their product.

    What is the Animal Rule?

  • The Animal Rule became law after 9/11 so that FDA can regulate countermeasures in animals, for conditions that are not ethical to apply to human volunteers, such as situations where biological or radiological agents are used against civilian populations. It is not ethical to apply these agents to any human volunteers just to see if a countermeasure may work. Some people call this the "Two Animal Rule" because typically the FDA would want the drug tested on at least two kinds of animals, on rodents and then on a larger animal (such as the mini-pig). The first group of tests will show "efficacy" that the drug can either mitigate the harm or even cure the disease. Then the drug manufacturer will need to show that the drug is safe in human volunteers (who are not exposed to the harm of the biological or radiological agent). The company product Fibrinogen-coated Albumin Sphere is fortunate in that it fits well within the Animal Rule and the conventional approach. Therefore, the company intends to use government grants to satisfy the requirements of the Animal Rule and to sell the product to the government (Strategic National Stockpile) for use in industrial and military applications where high doses of radiation is expected. The advantage is that the government grant will not dilute the company shares. The Phase I study will be essentially the same as the Phase I to be done under the regular clinical trials: the only difference is that the Indication for Animal Rule will be "Treatment of Radiation-induced Skin Injury after exposure to high radiation doses in Unexpected Situations" while the indication for the regular clinical trials will be "Treatment of Radiation-induced Skin Injury after exposure to low radiation doses in Radiation Therapy Patients."

    What is the difference between clinical trials Phase I, II and III?

  • The "conventional" approach to get FDA approval to market (sell) a drug is often described as Phase I, II, III. Before Fibroplate, Inc. can start human trials, the company will need to prepare an IND statement (Investigative New Drug) to notify the FDA of Fibroplate's intention to use FAS for the indication "Treatment of Radiation-induced Skin Injury". The company has essentially completed the IND, waiting only to fill in the exact Indication, which depends on which source of funding comes first. Phase I clinical trial will typically involve the recruitment of healthy volunteers so that any side effect of the new drug can be discovered. The dose is based on experience gained in previous animal studies. Even though animal studies may show that there are no obvious side effects with a "high dose" of a drug, Phase I human clinical trials will still have to be done. Phase II is aimed at finding the effective dose. Therefore, patients who have the illness to be cured will need to be enrolled. In a discussion with the clinical director at the Loma Linda University where they have a large population of radiation therapy patients, the director indicated to Dr. Yen that they can enroll enough patients for our study within weeks because 95% of all treated radiation therapy patient will show some skin injuries and lesions. Phase III is aimed at finding the safety and effectiveness of the Effective Dose on a large population. Again, we do not expect to need a long time to recruit enough patients for the study. Also, there is no other company that is trying to recruit the same group of patients to study their drug. There are at least 500,000 RSI patients every year in the USA, we will find enough patients who will enroll. After that the company will submit the data and ask FDA for marketing approval. After the product goes on the market, the FDA may demand that we follow up on the patients who receive the product (called Phase IV) in case some side effects are found only after giving the product to a very large group of patients after Phase III.

    How can we contact the company?

  • The company has a website www.fibroplate.com Meanwhile, contact Dr. Yen directly at DrRichardYen@Fibroplate.com.